European Journal of Neuroscience

Neural diseases are a major burden for society with respect to both health care cost and suffering of the affected individuals. Despite major efforts from the pharmaceutical industry there are almost no drugs to cure neural diseases. In my article I try to make the point that progress in drug development will require more investment in basic research. Better understanding of brain development and function will be the prerequisite to find cures and therapies for neural diseases in the future.

RNA-binding proteins (RBPs) exert crucial functions in mRNA localisation and in the control of local protein synthesis at the activated synapse. In this review, we outline the process of mRNA localisation and the role RBPs play in it. We further discuss how mis-regulation of many of these RBPs are linked to various neuronal diseases and how the latest advances in our understanding encourage early intervention strategies for treatment.

The study of Engrailed signaling in retinal axon guidance and in the survival of adult dopaminergic neurons has revealed an unsuspected link between a homeoprotein and mitochondrial activity. Engrailed-mediated effects involve translation regulation as well as cooperation with classical signaling pathways. These findings highlight the crucial role of cellular energy metabolism in neuron development, survival and neurodegeneration, and may help to identify novel therapeutic targets.

Brain development is associated with developmental sequences of voltage and transmitter gated currents and network patterns. We compare these sequences in different brain structures and show how they timely shift to behaviourally relevant ones for instance in the basal ganglia to enable targeted locomotion. In keeping with the ‘neuroarcheology’ concept, interruption or alteration of these sequences is a major signature of neurological disorders since neurons keep their immature features.

Translating basic science research into clinical practice involves overcoming multiple hurdles. Neonatal seizures have unique properties that have proved challenging for both clinicians and basic science researchers with new effective therapies developing slowly. This article will discuss barriers that exist for the development of new therapies for neonatal seizures and the challenges inherent in bringing new therapies from the bench to the bedside.

Cortical interneurons are affected in schizophrenia, and animal models reveal their protracted developmental trajectory is affected by diverse manipulations, yielding behavioral anomalies with a peri-adolescent onset. Immune activation and oxidative stress are likely factors that contribute to GABA interneuron alterations during development in these models and perhaps in schizophrenia as well. These observations suggest novel preventive approaches may be identified with translational efforts.

Schizophrenia is a common, usually chronic, and very costly illness with no proven means of prevention. Impairments in certain cognitive processes are the core feature of schizophrenia, reflect abnormalities in specific cortical circuits, and arise during childhood-adolescence. The implications of these findings for the development of preemptive, disease-modifying interventions in individuals at high risk for a clinical diagnosis of schizophrenia are discussed.

In this review we will discuss the current studies available in the literature regarding the genetics, pharmacogenomics and epigenetics of multiple sclerosis and propose an integrated view of disease pathogenesis, with the aim of opening a debate regarding the feasibility of future potential integrated approaches to therapy.

Mitochondrial sirtuins are NAD-dependent protein deacetylases associated with control of metabolism, aging and stem cell proliferation and differentiation. Their role in inflammatory demyelinating disease has not been fully characterised and is the subject of on-going research. Here, we expound the rationale behind selecting mitochondrial sirtuins as a therapeutic target in demyelinating disease.

Although Parkinson’s disease has been considered a pure motor disorder, cognitive impairment and depression are increasingly recognized non-motor symptoms with significant clinical impact. This review will focus on these neuropsychological symptoms and consider whether, and how, these deficits can best be modelled in rodent models of the disorder. Since only a few of these symptoms respond to dopamine-replacement therapies, the quest for other approaches remains a major research effort, and success in this area will be dependent on appropriate rodent models.

Many neurological diseases are manifested by changes in synaptic transmission and plasticity. As AMPA receptors are the workhorses in excitatory neurotransmission, we review the potential, as well as pitfalls, for targeting these receptors in four different neuropathologies.

In this review, we summarize recent findings about the role of cerebrovascular disease and vascular dysfunction as early events contributing to the progression of cognitive deficits and neurodegeneration in Alzheimer’s disease. We also discuss potential preventive therapies targeting these early vascular alterations.

Three-dimensional immunoelectron microscopy in the aging hippocampus reveals that neurons might utilise an extrusion mechanism to remove misfolded/damaged proteins which are then cleared by glia. This protective strategy appears to be impaired under chronic neuroinflammatory conditions, resulting in increased accumulation of aggregation-prone peptides and potentially facilitating the formation of amyloid plaques.