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Regulation of DNA methylation by ethanol induces tissue plasminogen activator expression in astrocytes

  1. Top of page
  2. Regulation of DNA methylation by ethanol induces tissue plasminogen activator expression in astrocytes
  3. A®40 modulates GABAA receptor 〈6 subunit expression and rat cerebellar granule neuron −maturation through the ERK/mTOR pathway
  4. GABAA receptor transmembrane amino acids are critical for alcohol action: disulfide cross-linking and alkyl methanethiosulfonate labeling reveal relative location of binding sites
  5. Molecular features of neural stem cells enable their enrichment using pharmacological inhibitors of survival-promoting kinases
  6. A conserved sequence in calmodulin regulated spectrin-associated protein 1 links its interaction with spectrin and calmodulin to neurite outgrowth
  7. Transglutaminase 2 accelerates neuroinflammation in amyotrophic lateral sclerosis through −interaction with misfolded superoxide dismutase 1
  8. A novel function for proSAAS as an amyloid anti-aggregant in Alzheimer's disease
  9. Changes in CNS cells in Hyperammonemic portal hypertensive rats
  10. Corticosterone administration up-regulated expression of norepinephrine transporter and −dopamine β-hydroxylase in rat locus coeruleus and its terminal regions
  11. Neuroprotective and anti-apoptotic effects of liraglutide on SH-SY5Y cells exposed to −methylglyoxal stress

We propose that ethanol, by decreasing DNMT-3a (DNA methyltransferase) levels and by inhibiting DNMT activity, reduces DNA methylation of the tissue plasminogen activator (tPA) promoter and leads to increased tPA mRNA and protein −expression in astrocytes; tPA released is also increased by ethanol. As tPA promotes the degradation of neuritogenic −extracellular matrix, the observed dysregulation of the epigenetic mechanism of DNA methylation in astyrocytes may be involved in ethanol-induced inhibition of astrocyte-mediated neuritogenesis.

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A®40 modulates GABAA receptor 〈6 subunit expression and rat cerebellar granule neuron −maturation through the ERK/mTOR pathway

  1. Top of page
  2. Regulation of DNA methylation by ethanol induces tissue plasminogen activator expression in astrocytes
  3. A®40 modulates GABAA receptor 〈6 subunit expression and rat cerebellar granule neuron −maturation through the ERK/mTOR pathway
  4. GABAA receptor transmembrane amino acids are critical for alcohol action: disulfide cross-linking and alkyl methanethiosulfonate labeling reveal relative location of binding sites
  5. Molecular features of neural stem cells enable their enrichment using pharmacological inhibitors of survival-promoting kinases
  6. A conserved sequence in calmodulin regulated spectrin-associated protein 1 links its interaction with spectrin and calmodulin to neurite outgrowth
  7. Transglutaminase 2 accelerates neuroinflammation in amyotrophic lateral sclerosis through −interaction with misfolded superoxide dismutase 1
  8. A novel function for proSAAS as an amyloid anti-aggregant in Alzheimer's disease
  9. Changes in CNS cells in Hyperammonemic portal hypertensive rats
  10. Corticosterone administration up-regulated expression of norepinephrine transporter and −dopamine β-hydroxylase in rat locus coeruleus and its terminal regions
  11. Neuroprotective and anti-apoptotic effects of liraglutide on SH-SY5Y cells exposed to −methylglyoxal stress

In addition to its neurotoxic role in Alzheimer's disease, A® is known to play important physiological roles. Whether A® improves neuronal development and maturation remains elusive. Our results demonstrate that low concentrations of A®40 significantly increase the GABAA receptor 6 subunit expression and associated current in cerebellar granule −neurons (CGNs) via the p75NTR and MEK/ERK pathway. A® also increases the thickness of the internal granule layer in APP−/− mice cerebellum. Our data provide new evidence for the role of A®40 in regulating the maturation of CGNs.

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GABAA receptor transmembrane amino acids are critical for alcohol action: disulfide cross-linking and alkyl methanethiosulfonate labeling reveal relative location of binding sites

  1. Top of page
  2. Regulation of DNA methylation by ethanol induces tissue plasminogen activator expression in astrocytes
  3. A®40 modulates GABAA receptor 〈6 subunit expression and rat cerebellar granule neuron −maturation through the ERK/mTOR pathway
  4. GABAA receptor transmembrane amino acids are critical for alcohol action: disulfide cross-linking and alkyl methanethiosulfonate labeling reveal relative location of binding sites
  5. Molecular features of neural stem cells enable their enrichment using pharmacological inhibitors of survival-promoting kinases
  6. A conserved sequence in calmodulin regulated spectrin-associated protein 1 links its interaction with spectrin and calmodulin to neurite outgrowth
  7. Transglutaminase 2 accelerates neuroinflammation in amyotrophic lateral sclerosis through −interaction with misfolded superoxide dismutase 1
  8. A novel function for proSAAS as an amyloid anti-aggregant in Alzheimer's disease
  9. Changes in CNS cells in Hyperammonemic portal hypertensive rats
  10. Corticosterone administration up-regulated expression of norepinephrine transporter and −dopamine β-hydroxylase in rat locus coeruleus and its terminal regions
  11. Neuroprotective and anti-apoptotic effects of liraglutide on SH-SY5Y cells exposed to −methylglyoxal stress

Alcohols modulate GABAA receptor function. The relative location of alcohol binding pockets in transmembrane domains was assessed by substituting critical amino acids with cysteines, and testing GABA responses and alcohol modulation before and after crosslinking double cysteine mutants and labeling single cysteine mutants. Lines show absence of −crosslinking (red), and crosslinking that modified GABA responses (black) and alcohol modulation (grey).

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Read the full article on page 363.

Molecular features of neural stem cells enable their enrichment using pharmacological inhibitors of survival-promoting kinases

  1. Top of page
  2. Regulation of DNA methylation by ethanol induces tissue plasminogen activator expression in astrocytes
  3. A®40 modulates GABAA receptor 〈6 subunit expression and rat cerebellar granule neuron −maturation through the ERK/mTOR pathway
  4. GABAA receptor transmembrane amino acids are critical for alcohol action: disulfide cross-linking and alkyl methanethiosulfonate labeling reveal relative location of binding sites
  5. Molecular features of neural stem cells enable their enrichment using pharmacological inhibitors of survival-promoting kinases
  6. A conserved sequence in calmodulin regulated spectrin-associated protein 1 links its interaction with spectrin and calmodulin to neurite outgrowth
  7. Transglutaminase 2 accelerates neuroinflammation in amyotrophic lateral sclerosis through −interaction with misfolded superoxide dismutase 1
  8. A novel function for proSAAS as an amyloid anti-aggregant in Alzheimer's disease
  9. Changes in CNS cells in Hyperammonemic portal hypertensive rats
  10. Corticosterone administration up-regulated expression of norepinephrine transporter and −dopamine β-hydroxylase in rat locus coeruleus and its terminal regions
  11. Neuroprotective and anti-apoptotic effects of liraglutide on SH-SY5Y cells exposed to −methylglyoxal stress

Neural stem cells resist death effectors, which contributes to their longevity. We demonstrate that primitive −Subventricular Zone neural precursors express low levels of pro-apoptotic molecules and resist PI3K (PD98059) and ERK1/2 (LY-294002) inhibition. By contrast, progenitors expressed higher levels of cell-death signaling molecules. Using combinations of PI3K and ERK1/2 inhibitors, cultures highly enriched in tripotential neural precursors were produced.

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Read the full article on page 376.

A conserved sequence in calmodulin regulated spectrin-associated protein 1 links its interaction with spectrin and calmodulin to neurite outgrowth

  1. Top of page
  2. Regulation of DNA methylation by ethanol induces tissue plasminogen activator expression in astrocytes
  3. A®40 modulates GABAA receptor 〈6 subunit expression and rat cerebellar granule neuron −maturation through the ERK/mTOR pathway
  4. GABAA receptor transmembrane amino acids are critical for alcohol action: disulfide cross-linking and alkyl methanethiosulfonate labeling reveal relative location of binding sites
  5. Molecular features of neural stem cells enable their enrichment using pharmacological inhibitors of survival-promoting kinases
  6. A conserved sequence in calmodulin regulated spectrin-associated protein 1 links its interaction with spectrin and calmodulin to neurite outgrowth
  7. Transglutaminase 2 accelerates neuroinflammation in amyotrophic lateral sclerosis through −interaction with misfolded superoxide dismutase 1
  8. A novel function for proSAAS as an amyloid anti-aggregant in Alzheimer's disease
  9. Changes in CNS cells in Hyperammonemic portal hypertensive rats
  10. Corticosterone administration up-regulated expression of norepinephrine transporter and −dopamine β-hydroxylase in rat locus coeruleus and its terminal regions
  11. Neuroprotective and anti-apoptotic effects of liraglutide on SH-SY5Y cells exposed to −methylglyoxal stress

Knockdown of the cytoskeletal protein CAMSAP1 using siRNA inhibited NGF-induced (nerve growth factor) neurite −outgrowth from PC12 cells, and axon production by cerebellar granule cells in culture. This activity is linked to a −spectrin- and Ca2+/calmodulin-binding region (CC1), since over-expression of isolated CC1 inhibited neurite production from PC12 cells. We previously showed that CAMSAP1 binds microtubules at the C-terminal CKK domain. Our data indicates −CAMSAP1 is a cytoskeletal interconnector required for neurite and axon production.

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Read the full article on page 391.

Transglutaminase 2 accelerates neuroinflammation in amyotrophic lateral sclerosis through −interaction with misfolded superoxide dismutase 1

  1. Top of page
  2. Regulation of DNA methylation by ethanol induces tissue plasminogen activator expression in astrocytes
  3. A®40 modulates GABAA receptor 〈6 subunit expression and rat cerebellar granule neuron −maturation through the ERK/mTOR pathway
  4. GABAA receptor transmembrane amino acids are critical for alcohol action: disulfide cross-linking and alkyl methanethiosulfonate labeling reveal relative location of binding sites
  5. Molecular features of neural stem cells enable their enrichment using pharmacological inhibitors of survival-promoting kinases
  6. A conserved sequence in calmodulin regulated spectrin-associated protein 1 links its interaction with spectrin and calmodulin to neurite outgrowth
  7. Transglutaminase 2 accelerates neuroinflammation in amyotrophic lateral sclerosis through −interaction with misfolded superoxide dismutase 1
  8. A novel function for proSAAS as an amyloid anti-aggregant in Alzheimer's disease
  9. Changes in CNS cells in Hyperammonemic portal hypertensive rats
  10. Corticosterone administration up-regulated expression of norepinephrine transporter and −dopamine β-hydroxylase in rat locus coeruleus and its terminal regions
  11. Neuroprotective and anti-apoptotic effects of liraglutide on SH-SY5Y cells exposed to −methylglyoxal stress

A new role of transglutaminase 2 (TG2) in misfolded SOD1-linked neuroinflammation has been clarified. TG2 recognized and oligomerized only misfolded forms of SOD1, which robustly activated microglia, and induce the expression of −proinflammatory molecules such as iNOS, IL-1®, and TNF-. The inhibition of spinal cord TG2 of mutant SOD1 transgenic mice successfully suppressed neuroinflammation and delayed the progression.

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Read the full article on page 403.

A novel function for proSAAS as an amyloid anti-aggregant in Alzheimer's disease

  1. Top of page
  2. Regulation of DNA methylation by ethanol induces tissue plasminogen activator expression in astrocytes
  3. A®40 modulates GABAA receptor 〈6 subunit expression and rat cerebellar granule neuron −maturation through the ERK/mTOR pathway
  4. GABAA receptor transmembrane amino acids are critical for alcohol action: disulfide cross-linking and alkyl methanethiosulfonate labeling reveal relative location of binding sites
  5. Molecular features of neural stem cells enable their enrichment using pharmacological inhibitors of survival-promoting kinases
  6. A conserved sequence in calmodulin regulated spectrin-associated protein 1 links its interaction with spectrin and calmodulin to neurite outgrowth
  7. Transglutaminase 2 accelerates neuroinflammation in amyotrophic lateral sclerosis through −interaction with misfolded superoxide dismutase 1
  8. A novel function for proSAAS as an amyloid anti-aggregant in Alzheimer's disease
  9. Changes in CNS cells in Hyperammonemic portal hypertensive rats
  10. Corticosterone administration up-regulated expression of norepinephrine transporter and −dopamine β-hydroxylase in rat locus coeruleus and its terminal regions
  11. Neuroprotective and anti-apoptotic effects of liraglutide on SH-SY5Y cells exposed to −methylglyoxal stress

In this study, we describe a novel anti-aggregant function for the neuroendocrine protein, proSAAS. We found that −proSAAS co-localizes with A® in Alzheimer's disease-affected brains, and co-immunoprecipitates with A® in brain −extracts. In vitro, proSAAS efficiently prevents A®1–42 fibrillation, and also blocks A®1–42–mediated neurotoxicity. These results suggest that proSAAS may be a novel target for neurodegenerative disease therapy.

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Read the full article on page 419.

Changes in CNS cells in Hyperammonemic portal hypertensive rats

  1. Top of page
  2. Regulation of DNA methylation by ethanol induces tissue plasminogen activator expression in astrocytes
  3. A®40 modulates GABAA receptor 〈6 subunit expression and rat cerebellar granule neuron −maturation through the ERK/mTOR pathway
  4. GABAA receptor transmembrane amino acids are critical for alcohol action: disulfide cross-linking and alkyl methanethiosulfonate labeling reveal relative location of binding sites
  5. Molecular features of neural stem cells enable their enrichment using pharmacological inhibitors of survival-promoting kinases
  6. A conserved sequence in calmodulin regulated spectrin-associated protein 1 links its interaction with spectrin and calmodulin to neurite outgrowth
  7. Transglutaminase 2 accelerates neuroinflammation in amyotrophic lateral sclerosis through −interaction with misfolded superoxide dismutase 1
  8. A novel function for proSAAS as an amyloid anti-aggregant in Alzheimer's disease
  9. Changes in CNS cells in Hyperammonemic portal hypertensive rats
  10. Corticosterone administration up-regulated expression of norepinephrine transporter and −dopamine β-hydroxylase in rat locus coeruleus and its terminal regions
  11. Neuroprotective and anti-apoptotic effects of liraglutide on SH-SY5Y cells exposed to −methylglyoxal stress

Rats with pre-hepatic portal hypertension because of partial portal vein ligation afford a model of minimal hepatic −encephalopathy that developed hyperammonemia. The cellular changes found here were similar to those described in ischemic conditions. Besides, a high expression of HIF-1 in cortical neurons was observed. It is likely that a hypoxia-like state is triggered via ammonia occupying the binding domain of HIF-1 and thereby preventing its degradation and −inducing its stabilization, leading to the over-expression of P-gp and the Epo-R.

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Read the full article on page 431.

Corticosterone administration up-regulated expression of norepinephrine transporter and −dopamine β-hydroxylase in rat locus coeruleus and its terminal regions

  1. Top of page
  2. Regulation of DNA methylation by ethanol induces tissue plasminogen activator expression in astrocytes
  3. A®40 modulates GABAA receptor 〈6 subunit expression and rat cerebellar granule neuron −maturation through the ERK/mTOR pathway
  4. GABAA receptor transmembrane amino acids are critical for alcohol action: disulfide cross-linking and alkyl methanethiosulfonate labeling reveal relative location of binding sites
  5. Molecular features of neural stem cells enable their enrichment using pharmacological inhibitors of survival-promoting kinases
  6. A conserved sequence in calmodulin regulated spectrin-associated protein 1 links its interaction with spectrin and calmodulin to neurite outgrowth
  7. Transglutaminase 2 accelerates neuroinflammation in amyotrophic lateral sclerosis through −interaction with misfolded superoxide dismutase 1
  8. A novel function for proSAAS as an amyloid anti-aggregant in Alzheimer's disease
  9. Changes in CNS cells in Hyperammonemic portal hypertensive rats
  10. Corticosterone administration up-regulated expression of norepinephrine transporter and −dopamine β-hydroxylase in rat locus coeruleus and its terminal regions
  11. Neuroprotective and anti-apoptotic effects of liraglutide on SH-SY5Y cells exposed to −methylglyoxal stress

Chronic stress and dysfunction of the noradrenergic system are etiologically related to depression. In an attempt to −explore their interaction, we found that chronic ingestion of corticosterone (CORT) up-regulated expression of −noradrenergic transporter (NET) and dopamine ®-hydroxylase (DBH) in the locus coeruleus and its main projection regions, which may induce an increase in cellular norepinephrine concentration. This interaction may represent an adaptive action to stress for maintaining homeostasis.

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Read the full article on page 445.

Neuroprotective and anti-apoptotic effects of liraglutide on SH-SY5Y cells exposed to −methylglyoxal stress

  1. Top of page
  2. Regulation of DNA methylation by ethanol induces tissue plasminogen activator expression in astrocytes
  3. A®40 modulates GABAA receptor 〈6 subunit expression and rat cerebellar granule neuron −maturation through the ERK/mTOR pathway
  4. GABAA receptor transmembrane amino acids are critical for alcohol action: disulfide cross-linking and alkyl methanethiosulfonate labeling reveal relative location of binding sites
  5. Molecular features of neural stem cells enable their enrichment using pharmacological inhibitors of survival-promoting kinases
  6. A conserved sequence in calmodulin regulated spectrin-associated protein 1 links its interaction with spectrin and calmodulin to neurite outgrowth
  7. Transglutaminase 2 accelerates neuroinflammation in amyotrophic lateral sclerosis through −interaction with misfolded superoxide dismutase 1
  8. A novel function for proSAAS as an amyloid anti-aggregant in Alzheimer's disease
  9. Changes in CNS cells in Hyperammonemic portal hypertensive rats
  10. Corticosterone administration up-regulated expression of norepinephrine transporter and −dopamine β-hydroxylase in rat locus coeruleus and its terminal regions
  11. Neuroprotective and anti-apoptotic effects of liraglutide on SH-SY5Y cells exposed to −methylglyoxal stress

We investigated the neuroprotective properties of the GLP-1 analogue liraglutide in SH-SY5Y cells during methyl glyoxal stress. Cell survival was enhanced, while cytotoxicity and apoptosis was reduced. Expression of the pro-survival Mcl1 signaling protein, activation of Akt, MEK1/2 and the transcription factor p90RSK was increased. Pro-apoptotic Bax and Bik expression was reduced, and the influx of calcium into the cell was normalised. The results demonstrate a range of growth factor related cytoprotective processes induced by the drug liraglutide.

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