Journal of Neurochemistry

Cover image for Vol. 137 Issue 5

Early View (Online Version of Record published before inclusion in an issue)

Edited By: Jörg Schulz

Impact Factor: 4.281

ISI Journal Citation Reports © Ranking: 2014: 56/252 (Neurosciences); 72/290 (Biochemistry & Molecular Biology)

Online ISSN: 1471-4159

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  1. 1 - 53
  1. Original Articles

    1. You have full text access to this OnlineOpen article
      Complex regulation of the regulator of synaptic plasticity histone deacetylase 2 in the rodent dorsal horn after peripheral injury

      Maria Maiarù, Oakley B. Morgan, Keri K. Tochiki, Eleanor J. Hobbiger, Kaveeta Rajani, Dorothy W. U. Overington and Sandrine M. Géranton

      Version of Record online: 27 MAY 2016 | DOI: 10.1111/jnc.13621

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      Our manuscript describes for the first time the regulation of the memory regulator histone deacetylase 2 (HDAC2) in the superficial dorsal horn of adult rats following peripheral injury. Our cell-specific approach has revealed a complex pattern of expression of spinal HDAC2 that depends on the injury and the cell type, suggesting a sophisticated regulation of gene expression by HDAC2.

    2. You have full text access to this OnlineOpen article
      Proteome rearrangements after auditory learning: high-resolution profiling of synapse-enriched protein fractions from mouse brain

      Thilo Kähne, Sandra Richter, Angela Kolodziej, Karl-Heinz Smalla, Rainer Pielot, Alexander Engler, Frank W. Ohl, Daniela C. Dieterich, Constanze Seidenbecher, Wolfgang Tischmeyer, Michael Naumann and Eckart D. Gundelfinger

      Version of Record online: 26 MAY 2016 | DOI: 10.1111/jnc.13636

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      How does the protein composition of synapses change in different brain areas upon auditory learning? We unravel discrete proteome changes in mouse auditory cortex, frontal cortex, hippocampus, and striatum functionally implicated in the learning process. We identify not only common but also area-specific biological pathways and cellular processes modulated 24 h after training, indicating individual contributions of the regions to memory processing.

    3. Probing amyloid-β pathology in transgenic Alzheimer's disease (tgArcSwe) mice using MALDI imaging mass spectrometry

      Louise Carlred, Wojciech Michno, Ibrahim Kaya, Peter Sjövall, Stina Syvänen and Jörg Hanrieder

      Version of Record online: 26 MAY 2016 | DOI: 10.1111/jnc.13645

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      Hanrieder et al. described an imaging mass spectrometry based study on comprehensive spatial profiling of C-terminally truncated Aβ species within individual plaques in tgArcSwe mice. Here, brain region-dependent differences in Aβ truncation and other plaque-associated proteins, such as macrophage migration inhibitory factor, were observed. The data shed further light on plaque-associated molecular mechanisms implicated in Alzheimer's pathogenesis.

    4. l-Lactate mediates neuroprotection against ischaemia by increasing TREK1 channel expression in rat hippocampal astrocytes in vitro

      Aditi Banerjee, Swagata Ghatak and Sujit Kumar Sikdar

      Version of Record online: 26 MAY 2016 | DOI: 10.1111/jnc.13638

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      Insufficient blood supply to the brain leads to cerebral ischaemia and increase in extracellular lactate concentrations. We incubated hippocampal astrocytes in lactate and observed increase in TREK1 channel expression via protein kinase A (PKA). Inhibition of TREK1, PKA and metabolic impairment of astrocytes prevented lactate from reducing cell death in ischaemic hippocampus. This pathway serves as an alternate mechanism of neuroprotection.

    5. Involvement of aberrant cyclin-dependent kinase 5/p25 activity in experimental traumatic brain injury

      Mohammad A. Yousuf, Chunfeng Tan, Melissa I. Torres-Altoro, Fang-Min Lu, Erik Plautz, Shanrong Zhang, Masaya Takahashi, Adan Hernandez, Steven G. Kernie, Florian Plattner and James A. Bibb

      Version of Record online: 25 MAY 2016 | DOI: 10.1111/jnc.13620

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      Traumatic brain injury (TBI) increases astrogliosis and microglial activation. Moreover, TBI deregulates Ca2+-homeostasis triggering p25 production. The protein kinase Cdk5 is aberrantly activated by p25 leading to phosphorylation of substrates including tau and Rb protein. Loss of Cdk5 attenuates TBI lesion size, indicating that Cdk5 is a critical player in TBI pathogenesis and thus may be a suitable therapeutic target for TBI.

  2. Reviews

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      Annexin A2, an essential partner of the exocytotic process in chromaffin cells

      Marion Gabel and Sylvette Chasserot-Golaz

      Version of Record online: 25 MAY 2016 | DOI: 10.1111/jnc.13628

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      Annexin A2 is a calcium-, actin-, and lipid-binding protein implicated in exocytosis in different cell types, including neuroendocrine cells. Upon cell stimulation, annexin A2 translocates from the cytosol to the plasma membrane of chromaffin cells and bundles actin filaments associated with chromaffin granules. This promotes the formation of lipid domains required for granule docking, and facilitates catecholamine release by compressing the granule.

  3. Original Articles

    1. Functional characterization of neurotransmitter activation and modulation in a nematode model ligand-gated ion channel

      Stephanie A. Heusser, Özge Yoluk, Göran Klement, Erika A. Riederer, Erik Lindahl and Rebecca J. Howard

      Version of Record online: 25 MAY 2016 | DOI: 10.1111/jnc.13644

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      In this study, we elucidate the validity of a modified glutamate-gated chloride channel (GluClcryst) as a structurally accessible model for GABAA receptors. In contrast to native-like controls, GluClcryst exhibits classical activation by its neurotransmitter ligand L-glutamate. The modified channel is also sensitive to allosteric modulators associated with human GABAA receptors, and to site-directed mutations predicted to alter channel opening.

    2. Role of serum- and glucocorticoid-inducible kinases in stroke

      Koichi Inoue, Tiandong Leng, Tao Yang, Zhao Zeng, Takatoshi Ueki and Zhi-Gang Xiong

      Version of Record online: 25 MAY 2016 | DOI: 10.1111/jnc.13650

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      To investigate the role of serum- and glucocorticoid-inducible kinases (SGKs) in ischemic brain injury, we examined how SGK inhibitors influence stroke outcome. Infarct volumes induced by middle cerebral artery occlusion were decreased significantly by SGK inhibitors. The inhibitors also reduced glutamate toxicity, at least partly, by attenuation of NMDA and voltage-gated sodium currents. Thus, SGK inhibition attenuates stroke damage.

    3. You have full text access to this OnlineOpen article
      Simvastatin inhibits neural cell apoptosis and promotes locomotor recovery via activation of Wnt/β-catenin signaling pathway after spinal cord injury

      Kai Gao, Zhaoliang Shen, Yajiang Yuan, Donghe Han, Changwei Song, Yue Guo and Xifan Mei

      Version of Record online: 23 MAY 2016 | DOI: 10.1111/jnc.13382

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      We verified the neuroprotective properties associated with simvastatin following spinal cord injury (SCI). Simvastatin reduced neuronal apoptosis, improved the functional and pathological recovery via activating Wnt/β-catenin signal pathway, however, the anti-apoptosis effects of simvastatin were reversed following suppressing Wnt/β-catenin signaling pathway in primary spinal cord neurons. The significant findings may provide clinical therapeutic value of simvastatin for treating SCI.

    4. Unusual social behavior in HPC-1/syntaxin1A knockout mice is caused by disruption of the oxytocinergic neural system

      Tomonori Fujiwara, Masumi Sanada, Takefumi Kofuji and Kimio Akagawa

      Version of Record online: 23 MAY 2016 | DOI: 10.1111/jnc.13634

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      Dopamine (DA) release is reduced in CNS of syntaxin1A null mutant mice (STX1A KO). Unusual social behavior was observed in STX1A KO. We found that oxytocin (OXT) release, which was stimulated by DA, was reduced and was rescued the unusual social behavior in STX1A KO was rescued by OXT. These results indicated that STX1A plays an important role in promoting social behavior through regulation of DA-induced OXT release in amygdala.

    5. Post-ischemic salubrinal treatment results in a neuroprotective role in global cerebral ischemia

      Berta Anuncibay-Soto, Diego Pérez-Rodríguez, María Santos-Galdiano, Enrique Font, Marta Regueiro-Purriños and Arsenio Fernández-López

      Version of Record online: 16 MAY 2016 | DOI: 10.1111/jnc.13651

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      The alleviation of ER stress by enhancing UPR with salubrinal treatment reduces the ischemic damage. This effect varies across the different neurovascular unit cell types. The salubrinal neuroprotective effect on CA1 supports differences in neurovascular unit for different brain regions and involves the inflammatory response and its time course. Thus, UPR modulation could be a therapeutic target in cerebral ischemia.

    6. Muscle biopsies from human muscle diseases with myopathic pathology reveal common alterations in mitochondrial function

      Balaraju Sunitha, Narayanappa Gayathri, Manish Kumar, Thottethodi Subrahmanya Keshava Prasad, Atchayaram Nalini, Balasundaram Padmanabhan and Muchukunte Mukunda Srinivas Bharath

      Version of Record online: 16 MAY 2016 | DOI: 10.1111/jnc.13626

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      We investigated whether human muscle diseases display mitochondrial changes. Muscle biopsies from dysferlinopathy (Dysfy), polymyositis (PM), and distal myopathy with rimmed vacuoles (DMRV) displayed morphological and biochemical evidences of mitochondrial dysfunction. Proteomic analysis revealed down-regulation of electron transport chain (ETC) subunits, assembly factors, and tricarboxylic acid (TCA) cycle enzymes, with 80 proteins common among the three pathologies. Mitochondrial proteins from muscle pathologies also displayed higher Trp oxidation that could alter the local structure.

    7. Mitigation of sensory and motor deficits by acrolein scavenger phenelzine in a rat model of spinal cord contusive injury

      Zhe Chen, Jonghyuck Park, Breanne Butler, Glen Acosta, Sasha Vega-Alvarez, Lingxing Zheng, Jonathan Tang, Robyn McCain, Wenpeng Zhang, Zheng Ouyang, Peng Cao and Riyi Shi

      Version of Record online: 16 MAY 2016 | DOI: 10.1111/jnc.13639

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      We have shown that phenelzine can attenuate neuropathic pain behavior in acute, delayed, and chronic administration in post-SCI rats. This was accompanied by a dose-dependent reduction in an acrolein metabolite in urine and an acrolein adduct in spinal cord tissue, and the suppression of TRPA1 over-expression in central and peripheral locations post-trauma. Acrolein scavenging might be a novel therapeutic strategy to reduce post-SCI neuropathic pain.

    8. Myosin light chain kinase facilitates endocytosis of synaptic vesicles at hippocampal boutons

      Lin Li, Xiaomei Wu, Hai-Yuan Yue, Yong-Chuan Zhu and Jianhua Xu

      Version of Record online: 16 MAY 2016 | DOI: 10.1111/jnc.13635

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      The kinetics of vesicle membrane endocytosis at nerve terminals has long been known to depend on activity and Ca2+. This study provides evidence suggesting that myosin light chain kinase increases endocytosis efficiency at hippocampal neurons by mediating Ca2+/calmodulin-dependent phosphorylation of myosin. The authors propose that this signal cascade may serve as a common pathway contributing to the activity-dependent regulation of vesicle endocytosis at synapses.

    9. cGMP/cGMP-dependent protein kinase pathway modulates nicotine-induced currents through the activation of α-bungarotoxin-insensitive nicotinic acetylcholine receptors from insect neurosecretory cells

      Safa Mannai, Lofti Bitri and Steeve H. Thany

      Version of Record online: 12 MAY 2016 | DOI: 10.1111/jnc.13633

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      We propose that nicotinic acetylcholine receptor activation induces an increase in intracellular calcium (Ca2+) concentration. Elevation of intracellular Ca2+ results in the formation of Ca2+-calmodulin (CaM) complex, which activates guanylyl cyclase (GC) and/or adenylyl cyclase (AC). Ca2+-CaM complex could activate Ca2+ calmodulin kinase II which could directly or indirectly modulate the nicotinic response. The mechanisms by which cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) interact remain unclear. We demonstrate that nicotine-induced currents are coupled to the cGMP/PKG pathway.

  4. Short Communications

    1. Limited predictability of postmortem human brain tissue quality by RNA integrity numbers

      Kai-C. Sonntag, George Tejada, Sivan Subburaju, Sabina Berretta, Francine M. Benes and Tsung-Ung W. Woo

      Version of Record online: 12 MAY 2016 | DOI: 10.1111/jnc.13637

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      Quality assessment of postmortem human brains by RNA integrity numbers (RINs) may be misleading, as they do not measure intact mRNAs. We show that the RIN is an indicator of mRNA quantity independent of degradation, but does not predict mRNA integrity, suggesting that RINs provide an incomplete measure of brain tissue quality. Our results resolve controversial assumption on interpreting quality assessments of human postmortem brains by RINs.

  5. Original Articles

    1. Elucidation of the interplay between Fe(II), Fe(III), and dopamine with relevance to iron solubilization and reactive oxygen species generation by catecholamines

      Yingying Sun, A. Ninh Pham and T. David Waite

      Version of Record online: 12 MAY 2016 | DOI: 10.1111/jnc.13615

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      Powerful oxidants such as the hydroxyl radical (OH) have previously been thought to be generated through the interplay between dopamine (DA) and iron, contributing to damage to cells and, potentially, leading to neuronal degenerative diseases such as Parkinson's disease. Our results suggest that DA plays a dual role as high DA/Fe(II) ratios prevent Fe(II) from reacting with the generated H2O2 thereby reducing OH generation, whereas low DA/Fe(II) ratios enhance OH generation as a result of reaction of unbound Fe(II) and H2O2 produced via both autoxidation and iron-catalyzed oxidation of DA.

  6. Reviews

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      How can rAAV-α-synuclein and the fibril α-synuclein models advance our understanding of Parkinson's disease?

      Laura A. Volpicelli-Daley, Deniz Kirik, Lindsay E. Stoyka, David G. Standaert and Ashley S. Harms

      Version of Record online: 4 MAY 2016 | DOI: 10.1111/jnc.13627

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      This review describes two α-synuclein-based rodent models of Parkinson's disease: the rAAV-α-synuclein model and the α-synuclein fibril model. The key features of these models are described, and the extent to which they recapitulate features of PD, such as α-synuclein inclusion formation, loss of dopaminergic synapses in the striatum, motor defects, inflammation, and dopamine neuron death.

      This article is part of a special issue on Parkinson disease.

  7. Past to Future

    1. Synaptic signalling and its interface with neuropathologies: snapshots from the past, present and future

      Philip M. Beart

      Version of Record online: 4 MAY 2016 | DOI: 10.1111/jnc.13598

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      Highlighted are important advances in synaptic signalling over the last decade in the Journal of Neurochemistry. Across all transmitter systems elucidation of circuit function, and notably molecular insights, have underpinned remarkable growth in the identification of targets likely to provide therapeutic benefit in neuropathologies. Another commonality was wide interest in forebrain circuitry and its tonic excitatory control. Increasingly observations relate to signalling in disease and behavioural conditions.

      This article is part of the 60th Anniversary special issue.

    2. Neuroinflammation: the devil is in the details

      Damon J. DiSabato, Ning Quan and Jonathan P. Godbout

      Version of Record online: 4 MAY 2016 | DOI: 10.1111/jnc.13607

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      In this review, we will use brain and spinal cord injury, stress, aging, and other inflammatory events to illustrate the potential harm and benefits inherent to neuroinflammation. Context, course, and duration of the inflammation are highly important to the interpretation of these events, and we aim to provide insight into this by detailing several commonly studied insults.

      This article is part of the 60th anniversary supplemental issue.

  8. Bench to Bedside

    1. Overcoming translational barriers impeding development of Alzheimer's disease modifying therapies

      Todd E. Golde

      Version of Record online: 4 MAY 2016 | DOI: 10.1111/jnc.13583

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      Seminal discoveries made over the past 25 years have provided firm rationale for a new generation of Alzheimer's disease (AD) therapies designed as disease modifying agents that would slow or even reverse the disease course. Unfortunately, no therapy has yet to show significant clinical disease modification. In this review, I describe 10 translational barriers to successful AD disease modification, highlight current efforts addressing some of these barriers, and discuss how the field could focus future efforts to overcome these barriers.

      This article is part of the 60th Anniversary special issue.

    2. Hippocampal metabotropic glutamate receptor long-term depression in health and disease: focus on mitogen-activated protein kinase pathways

      Thomas M. Sanderson, Ellen L. Hogg, Graham L. Collingridge and Sonia A. L. Corrêa

      Version of Record online: 4 MAY 2016 | DOI: 10.1111/jnc.13592

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      mGluR-LTD is a form of synaptic plasticity that impacts on memory formation. In the hippocampus mitogen-activated protein kinases (MAPKs) have been found to be important in mGluR-LTD. In this 60th anniversary special issue article, we review the independent and complementary roles of two classes of MAPK, p38 and ERK1/2 and link this to the aberrant mGluR-LTD that has an important role in diseases.

      This article is part of the 60th Anniversary special issue.

  9. Reviews

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      The intravesicular cocktail and its role in the regulation of exocytosis

      Judith Estévez-Herrera, Ayoze González-Santana, Rebeca Baz-Dávila, José D. Machado and Ricardo Borges

      Version of Record online: 2 MAY 2016 | DOI: 10.1111/jnc.13609

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      In this review, we have highlighted the mechanisms that permit the storage of neurotransmitters and hormones inside secretory vesicles. We also have proposed a novel model based in the intravesicular interactions of the main components of this inner cocktail – catecholamines, ATP, and chromogranins – to allow the accumulation of near molar concentrations of transmitters in secretory vesicles.

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      Exocytosis in non-neuronal cells

      Peter Thorn, Robert Zorec, Jens Rettig and Damien J. Keating

      Version of Record online: 2 MAY 2016 | DOI: 10.1111/jnc.13602

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      Non-neuronal cells have acquired highly specialized mechanisms to control the release of unique chemical messengers, such as polarised fusion of insulin granules in pancreatic β cells targeted towards the vasculature (top). This review discusses mechanisms used in several important non-neuronal cell types to control exocytosis, and the relevance of intermediate vesicle fusion pore states (bottom) and their specialized output to the physiological role of each cell type. These include enteroendocrine cells, pancreatic β cells, astrocytes, lactotrophs and cytotoxic T lymphocytes.

    3. You have free access to this content
      Lipids implicated in the journey of a secretory granule: from biogenesis to fusion

      Emeline Tanguy, Ophélie Carmon, Qili Wang, Lydie Jeandel, Sylvette Chasserot-Golaz, Maité Montero-Hadjadje and Nicolas Vitale

      Version of Record online: 2 MAY 2016 | DOI: 10.1111/jnc.13577

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      In this review, we highlight evidence supporting the notion that lipids play important functions in secretory vesicle biogenesis, maturation, recruitment, and membrane fusion steps. These effects include regulating various protein distribution and activity, but also directly modulating membrane topology. The challenges ahead to understand the pleiotropic functions of lipids in a secretory granule's journey are also discussed.

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      How the stimulus defines the dynamics of vesicle pool recruitment, fusion mode, and vesicle recycling in neuroendocrine cells

      Ana María Cárdenas and Fernando D. Marengo

      Version of Record online: 2 MAY 2016 | DOI: 10.1111/jnc.13565

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      In chromaffin cells, a brief stimulus induces the exocytosis of a small pool of vesicles that is highly coupled to voltage-dependent Ca2+ channels (A), whereas longer or high-frequency stimulation provokes a global Ca2+ increase, promoting exocytosis irrespective of vesicle location (B). Furthermore, low-frequency stimulation favors kiss-and-run exocytosis (A), whereas higher frequencies promote full fusion (B). In this review, we analyze the mechanisms by which a given stimulation pattern defines the mode of exocytosis, and recruitment and recycling of neurosecretory vesicles.

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      Unproductive exocytosis

      Marko Kreft, Jernej Jorgačevski, Nina Vardjan and Robert Zorec

      Version of Record online: 1 MAY 2016 | DOI: 10.1111/jnc.13561

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      The fusion pore is a channel that forms when the vesicle and the plasma membranes merge, and mediates the release of secretions from the vesicle lumen to the cell exterior. Frequently, these pores are too narrow to pass molecules to the extracellular space. Anisotropic membrane constituents with a non-axisymmetric shape were proposed to accumulate in the fusion pore membrane.

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      F-actin cytoskeleton and the fate of organelles in chromaffin cells

      José Villanueva, Yolanda Gimenez-Molina, Salvador Viniegra and Luis M. Gutiérrez

      Version of Record online: 1 MAY 2016 | DOI: 10.1111/jnc.13560

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      In chromaffin cells, organelles such as granules and mitochondria distribute forming cortical and perinuclear populations whereas others like the ER present homogenous distributions. In the present review we discuss the role of transport systems and the existence of an F-actin cortical structure as the main factors behind the formation of organelle subpopulations in this neuroendocrine cell model.

  10. Original Articles

    1. Oligomerization of the microtubule-associated protein tau is mediated by its N-terminal sequences: implications for normal and pathological tau action

      H. Eric Feinstein, Sarah J. Benbow, Nichole E. LaPointe, Nirav Patel, Srinivasan Ramachandran, Thanh D. Do, Michelle R. Gaylord, Noelle E. Huskey, Nicolette Dressler, Megan Korff, Brady Quon, Kristi Lazar Cantrell, Michael T. Bowers, Ratnesh Lal and Stuart C. Feinstein

      Version of Record online: 20 APR 2016 | DOI: 10.1111/jnc.13604

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      The microtubule-associated protein tau is essential for neuronal development and maintenance, but is also central to Alzheimer's and related dementias. Unfortunately, the molecular mechanisms underlying normal and pathological tau action remain poorly understood. Here, we demonstrate that tau can homo-oligomerize, providing novel mechanistic models for normal tau action (promoting microtubule growth and bundling, suppressing microtubule shortening) and pathological tau action (poisoning of oligomeric complexes).

  11. Reviews

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      Genetics in Parkinson disease: Mendelian versus non-Mendelian inheritance

      Dena G. Hernandez, Xylena Reed and Andrew B. Singleton

      Version of Record online: 18 APR 2016 | DOI: 10.1111/jnc.13593

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      This review discusses monogenic risk factors and mechanisms of Mendelian inheritance of Parkinson disease. Highly penetrant mutations in SNCA, Parkin, DJ-1, PINK 1, LRRK2 and VPS35 produce rare, monogenic forms of the disease, while unique variants within LRRK2 and GBA show incomplete penetrance and are strong risk factors for PD. Additionally, over 20 common variants with small effect sizes modulate disease risk. The challenge over the next decade is to strengthen genetic findings by assessing direct, biological consequences of risk variants in tandem with high-content, integrated datasets.

      This article is part of a special issue on Parkinson disease.

    2. You have free access to this content
      Cellular models for Parkinson's disease

      Björn H. Falkenburger, Theodora Saridaki and Elisabeth Dinter

      Version of Record online: 18 APR 2016 | DOI: 10.1111/jnc.13618

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      Cellular models reproduce the two most salient changes of Parkinson's disease, the degeneration of dopaminergic neurons and the existence of α-synuclein aggregates. This article is intended for researchers planning to use cellular models for their studies. It describes for commonly used cell types and treatments the aspects of Parkinson's disease they model along with technical advantages and disadvantages. Furthermore, this article describes strategies to induce and measure aggregates with a focus on fluorescent techniques.

      This article is part of a special issue on Parkinson disease.

    3. You have free access to this content
      ɑ-Synuclein strains and the variable pathologies of synucleinopathies

      Wouter Peelaerts and Veerle Baekelandt

      Version of Record online: 30 MAR 2016 | DOI: 10.1111/jnc.13595

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      Parkinson's disease and other synucleinopathies share ɑ-synuclein deposits as a common histopathological hallmark. New and ongoing developments are now showing that variations in the aggregation process and the formation of ɑ-synuclein strains may be paralleled by the development of distinct synucleinopathies. Here, we review the recent developments and the role of strains in synucleinopathies.

      This article is part of a special issue on Parkinson disease.

    4. You have full text access to this OnlineOpen article
      Converging roles of ion channels, calcium, metabolic stress, and activity pattern of Substantia nigra dopaminergic neurons in health and Parkinson's disease

      Johanna Duda, Christina Pötschke and Birgit Liss

      Version of Record online: 23 MAR 2016 | DOI: 10.1111/jnc.13572

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      We propose that SN DA neurons possess several feedback and feed-forward mechanisms to protect and adapt their activity-pattern and calcium-homeostasis within a physiological bandwidth, and that PD-trigger factors can narrow this bandwidth. We summarize roles of ion channels in this view, and findings documenting that both, reduced as well as elevated activity and associated calcium-levels can trigger SN DA degeneration.

      This article is part of a special issue on Parkinson disease.

    5. You have free access to this content
      MMP-9 in translation: from molecule to brain physiology, pathology, and therapy

      Behnam Vafadari, Ahmad Salamian and Leszek Kaczmarek

      Version of Record online: 21 MAR 2016 | DOI: 10.1111/jnc.13415

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      MMP-9, through cleavage of specific target proteins, plays a major role in synaptic plasticity and neuroinflammation, and by those virtues contributes to brain physiology and a host of neurological and psychiatric disorders.

      This article is part of the 60th Anniversary special issue.

    6. You have free access to this content
      ‘From past to future’ – deciphering the molecular basis of Alzheimer's disease through the pages of the Journal of Neurochemistry

      Roberto Cappai

      Version of Record online: 21 MAR 2016 | DOI: 10.1111/jnc.13546

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      The Journal of Neurochemistry has made significant contributions toward unraveling the molecular, cellular and pathological basis of Alzheimer's disease through its 60 years.

      This article is part of the 60th Anniversary special issue.

    7. You have free access to this content
      The challenges for scientific publishing, 60 years on

      Laura Hausmann, Sean P. Murphy and on behalf of the Publication Committee of the International Society for Neurochemistry (ISN)

      Version of Record online: 21 MAR 2016 | DOI: 10.1111/jnc.13550

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      In the past decades, science publishing underwent dramatic changes in the communication of data and in their interpretation, in the increasing pressure and commercialization, and the democratization of science on a global scale via the Internet. This article reviews the benefits and challenges to publishing including fraudulent behavior and plagiarism, data and statistics reporting standards, authorship confirmation and other issues, with the aim to provide readers with practical examples and hands-on guidelines. As we illustrate here, identifying unacceptable practices leads to changes in the standards for data reporting.

      This article is part of the 60th Anniversary special issue.

  12. Editorial Highlights

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      The ABCD's of 5′-adenosine monophosphate-activated protein kinase and adrenoleukodystrophy

      Ian Weidling and Russell H. Swerdlow

      Version of Record online: 15 MAR 2016 | DOI: 10.1111/jnc.13594

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      This Editorial highlights a study by Singh and coworkers in the current issue of Journal of Neurochemistry, in which the authors present additional evidence that AMPKα1 is reduced in X-linked adrenoleukodystrophy (X-ALD). They make a case for increasing AMPKα1 activity for therapeutic purposes in this disease, and indicate how this goal may be achieved.

      Read the highlighted article ‘Metformin-induced mitochondrial function and ABCD2 up regulation in X-linked adrenoleukodystrophy involves AMP activated protein kinase’ on doi: 10.1111/jnc.13562.

  13. Original Articles

    1. Metformin-induced mitochondrial function and ABCD2 up-regulation in X-linked adrenoleukodystrophy involves AMP-activated protein kinase

      Jaspreet Singh, Brittany Olle, Hamid Suhail, Michelle M. Felicella and Shailendra Giri

      Version of Record online: 14 MAR 2016 | DOI: 10.1111/jnc.13562

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      There is no effective therapy for inherited peroxisomal disorder X-linked adrenoleukodystrophy (X-ALD). We document the therapeutic potential of FDA approved drug, Metformin, for X-ALD by targeting AMPK. Metformin induced peroxisomal Abcd2 levels in vitro and in vivo. Metformin lowered VLCFA levels, improved mitochondrial function and ameliorated inflammatory gene expression in X-ALD patient-derived cells. Metformin-induced Abcd2 levels were dependent on AMPKα1, a metabolic and anti-inflammatory gene, recently documented by our laboratory to play a putative role in X-ALD pathology.

      Read the Editorial Highlight for this article on doi: 10.1111/jnc.13594.

  14. Reviews

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      Neural plasticity and behavior – sixty years of conceptual advances

      J. David Sweatt

      Version of Record online: 10 MAR 2016 | DOI: 10.1111/jnc.13580

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      The area of neural plasticity and behavior has seen tremendous advances over the last six decades, with many of those advances being specifically in the neurochemistry domain. This review provides an overview of the progress in the area of neuroplasticity and behavior over the life-span of the Journal of Neurochemistry. To organize the broad literature base, the review collates progress into fifteen broad categories identified as ‘conceptual advances’, as viewed by the author. The fifteen areas are delineated in the figure above.

      This article is part of the 60th Anniversary special issue.

  15. Bench to Bedside

    1. Bioenergetics and metabolism: a bench to bedside perspective

      Russell H. Swerdlow

      Version of Record online: 10 MAR 2016 | DOI: 10.1111/jnc.13509

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      A bench-to-bedside biomedical research process is discussed that moves through conceptual, basic, translational, and clinical levels. For example, herein a case was made that bioenergetics is a valid Alzheimer's disease therapeutic target. Following this, a fundamental strategy for manipulating bioenergetics was defined, potential implications studied, and the approach extended to the clinical arena.

      This article is part of the 60th Anniversary special issue.

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      The next step in translational research: lessons learned from the first preclinical randomized controlled trial

      Gemma Llovera and Arthur Liesz

      Version of Record online: 10 MAR 2016 | DOI: 10.1111/jnc.13516

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      Translational research is hampered by low reproducibility of preclinical studies and countless failed clinical trials. International consortia have proposed preclinical multicenter trials as an intermediate step to overcome this ‘translational roadblock’. We have recently performed the first such preclinical randomized controlled trial (pRCT) by adopting key elements of clinical study design to preclinical research. In this review, we discuss the lessons learned from this trial and provide suggestions how to optimize future pRCTs.

      This article is part of the 60th Anniversary special issue.

    3. Causes, consequences, and cures for neuroinflammation mediated via the locus coeruleus: noradrenergic signaling system

      Douglas L. Feinstein, Sergey Kalinin and David Braun

      Version of Record online: 10 MAR 2016 | DOI: 10.1111/jnc.13447

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      The classical neurotransmitter noradrenaline (NA) has critical roles in modulating behaviors including those involved in sleep, anxiety, and depression. However, NA can also elicit anti-inflammatory responses in glial cells, can increase neuronal viability by inducing neurotrophic factor expression, and can reduce neuronal damage due to oxidative stress by scavenging free radicals. NA is primarily produced by tyrosine hydroxylase (TH) expressing neurons in the locus coeruleus (LC), a relatively small brainstem nucleus near the IVth ventricle which sends projections throughout the brain and spinal cord. It has been known for close to 50 years that LC neurons are lost during normal aging, and that loss is exacerbated in neurological diseases including Parkinson's disease and Alzheimer's disease. LC neuronal damage and glial activation has now been documented in a variety of other neurological conditions and diseases, however, the causes of LC damage and cell loss remain largely unknown. A number of approaches have been developed to address the loss of NA and increased inflammation associated with LC damage, and several methods are being explored to directly minimize the extent of LC neuronal cell loss or function. In this review, we will summarize some of the consequences of LC loss, consider several factors that likely contribute to that loss, and discuss various ways that have been used to increase NA or to reduce LC damage.

      This article is part of the 60th Anniversary special issue.

  16. Past to Future

    1. Proteoglycans and axon guidance: a new relationship between old partners

      Masayuki Masu

      Version of Record online: 10 MAR 2016 | DOI: 10.1111/jnc.13508

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      Neural circuits are formed by the combined actions of axon guidance molecules. Proteoglycans play critical roles in regulating axon guidance through the interaction between signaling molecules and glycosaminoglycan chains attached to the core protein. This paper summarizes the structure and functions of axon guidance molecules and glycosaminoglycans and reviews the molecular mechanisms by which proteoglycans regulate axon guidance from a new vantage point.

      This article is part of the 60th Anniversary special issue.

  17. Supplement Articles

    1. You have full text access to this OnlineOpen article
      Bioenergetics and redox adaptations of astrocytes to neuronal activity

      Juan P. Bolaños

      Version of Record online: 10 MAR 2016 | DOI: 10.1111/jnc.13486

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      Our current knowledge on brain's management of bioenergetics and redox requirements associated with neural activity is herein revisited. The astrocyte-neuronal lactate shuttle (ANLS) explains the energy needs of neurotransmission. Furthermore, neurotransmission unavoidably triggers increased mitochondrial reactive oxygen species in neurons. By coupling glutamatergic activity with transcriptional activation of antioxidant genes, astrocytes provide neurons with neuroprotective glutathione through an astrocyte-neuronal glutathione shuttle (ANGS).

      This article is part of the 60th Anniversary special issue.

  18. Editorial

    1. You have free access to this content
      LRRK2 pathobiology in Parkinson's disease – virtual inclusion

      Ian Martin, Jungwoo Wren Kim, Valina L. Dawson and Ted M. Dawson

      Version of Record online: 22 FEB 2016 | DOI: 10.1111/jnc.13549

      This article is part of a special issue on Parkinson disease.

  19. Reviews

    1. You have free access to this content
      Sorting out release, uptake and processing of alpha-synuclein during prion-like spread of pathology

      Trevor Tyson, Jennifer A. Steiner and Patrik Brundin

      Version of Record online: 10 FEB 2016 | DOI: 10.1111/jnc.13449

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      The prion-like hypothesis of α-synuclein pathology suggests a method for the transmission of misfolded α-synuclein from one neuron to another. This hypothesis postulates that misfolded α-synuclein becomes aggregation prone and when released and taken up by neighboring cells, seeds further misfolding and aggregation. In this review we examine the cellular mechanisms that are involved in the processing of α-synuclein and how these may contribute to the prion-like propagation of α-synuclein pathology.

      This article is part of a special issue on Parkinson disease.

  20. Systematic Reviews

    1. You have free access to this content
      Parkinson's disease: acid-glucocerebrosidase activity and alpha-synuclein clearance

      Judith Blanz and Paul Saftig

      Version of Record online: 10 FEB 2016 | DOI: 10.1111/jnc.13517

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      Lysosomes are critical for protein and lipid homeostasis. Recent research revealed that dysfunction of this organelle contributes to the development of neurodegenerative diseases such as Parkinson's disease (PD). Mutations in the lysosomal hydrolase β-glucocerebrosidase (GBA1) are a major risk factor for the development of PD and the molecular events linked to the reduced activity of GBA1 and the pathological accumulation of lipids and α-synuclein are just at the beginning to be understood. New therapeutic concepts in regards to how to increase the expression, stability, or delivery of β-glucocerebrosidase to lysosomes are currently developed.

      This article is part of a special issue on Parkinson disease.

  21. Reviews

    1. You have free access to this content
      Therapeutic approaches in Parkinson's disease and related disorders

      Elvira Valera and Eliezer Masliah

      Version of Record online: 10 FEB 2016 | DOI: 10.1111/jnc.13529

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      Synucleinopathies, neurodegenerative disorders characterized by the abnormal accumulation of the protein alpha-synuclein, constitute the second leading cause of parkinsonism and dementia in the elderly population, however, no disease-modifying options are available yet. In this review, we summarize the therapeutic approaches currently being explored for synucleinopathies, suggest possible explanations to the clinical outcomes, and propose areas of further therapeutic improvement.

      This article is part of a special issue on Parkinson disease.

    2. You have free access to this content
      Iron neurochemistry in Alzheimer's disease and Parkinson's disease: targets for therapeutics

      Abdel A. Belaidi and Ashley I. Bush

      Version of Record online: 10 FEB 2016 | DOI: 10.1111/jnc.13425

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      Iron plays a fundamental role in maintaining the high metabolic and energetic requirements of the brain. However, iron has to be maintained in a delicate balance as both iron overload and iron deficiency are detrimental to the brain and can trigger neurodegeneration. Here, we discuss the current knowledge on brain iron homeostasis and its involvement in major aging-related neurodegenerative diseases.

      This article is part of a special issue on Parkinson disease.

    3. You have free access to this content
      Biological confounders for the values of cerebrospinal fluid proteins in Parkinson's disease and related disorders

      Brit Mollenhauer, Lucilla Parnetti, Irena Rektorova, Milica G. Kramberger, Maria Pikkarainen, Walter J. Schulz-Schaeffer, Dag Aarsland, Per Svenningsson, Lucia Farotti, Marcel M. Verbeek and Michael G. Schlossmacher

      Version of Record online: 10 FEB 2016 | DOI: 10.1111/jnc.13390

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      Cerebrospinal fluid (CSF) has been extensively studied to explore biochemical alterations in subjects with neurodegenerative disorders. To investigate potential biological confounders of reported CSF levels for α-synuclein (α-Syn), amyloid-β 1-42(Aβ42) and tau protein in Parkinson's disease and related disorders, we reviewed the current literature for known factors that underlie signal variability and speculate on those that have not yet been tested.

  22. Original Articles

    1. The relationship between glucocerebrosidase mutations and Parkinson disease

      Anna Migdalska-Richards and Anthony H. V. Schapira

      Version of Record online: 10 FEB 2016 | DOI: 10.1111/jnc.13385

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      The impact of glucocerebrosidase 1 (GBA1) mutations on functioning of endoplasmic reticulum (ER), lysosomes, and mitochondria. GBA1 mutations resulting in production of misfolded glucocerebrosidase (GCase) significantly affect the ER functioning. Misfolded GCase trapped in the ER leads to both an increase in the ubiquitin–proteasome system (UPS) and the ER stress. The presence of ER stress triggers the unfolded protein response (UPR) and/or endoplasmic reticulum-associated degradation (ERAD). The prolonged activation of UPR and ERAD subsequently leads to increased apoptosis. The presence of misfolded GCase in the lysosomes together with a reduction in wild-type GCase levels lead to a retardation of alpha-synuclein degradation via chaperone-mediated autophagy (CMA), which subsequently results in alpha-synuclein accumulation and aggregation. Impaired lysosomal functioning also causes a decrease in the clearance of autophagosomes, and so their accumulation. GBA1 mutations perturb normal mitochondria functioning by increasing generation of free radical species (ROS) and decreasing adenosine triphosphate (ATP) production, oxygen consumption, and membrane potential. GBA1 mutations also lead to accumulation of dysfunctional and fragmented mitochondria.

      This article is part of a special issue on Parkinson disease.

  23. Reviews

    1. You have free access to this content
      Structure, function and toxicity of alpha-synuclein: the Bermuda triangle in synucleinopathies

      Anna Villar-Piqué, Tomás Lopes da Fonseca and Tiago Fleming Outeiro

      Version of Record online: 11 SEP 2015 | DOI: 10.1111/jnc.13249

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      Alpha-synuclein is the speculated cornerstone of several neurodegenerative disorders known as Synucleinopathies. Nevertheless, the mechanisms underlying the pathogenic effects of this protein remain unknown. Here, we review the recent findings in the three corners of alpha-synuclein biology – structure, function and toxicity – and discuss the enigmatic roads that have accompanied alpha-synuclein from the beginning.

    2. You have free access to this content
      Genes associated with Parkinson's disease: regulation of autophagy and beyond

      Alexandra Beilina and Mark R Cookson

      Version of Record online: 3 SEP 2015 | DOI: 10.1111/jnc.13266

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      Beilina and Cookson review the links between genes for Parkinson's disease (red) and the autophagy–lysosomal system. They propose the hypothesis that many of the known PD genes can be assigned to pathways that affect (I) turnover of mitochondria via mitophagy (II) turnover of several vesicular structures via macroautophagy or chaperone-mediated autophagy or (III) general lysosome function.

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