Axon guidance proteins in neurological disorders.
Lancet Neurol. 2015 May;14(5):532-46
Authors: Van Battum EY, Brignani S, Pasterkamp RJ
Many neurological disorders are characterised by structural changes in neuronal connections, ranging from presymptomatic synaptic changes to the loss or rewiring of entire axon bundles. The molecular mechanisms that underlie this perturbed connectivity are poorly understood, but recent studies suggest a role for axon guidance proteins. Axon guidance proteins guide growing axons during development and control structural plasticity of synaptic connections in adults. Changes in expression or function of these proteins might induce pathological changes in neural circuits that predispose to, or cause, neurological diseases. For some neurological disorders, such as midline crossing disorders, investigators have identified causative mutations in genes for axon guidance. However, for most other disorders, evidence is correlative and further studies are needed to confirm the pathological role of defects in proteins for axon guidance. Importantly, further insight into how dysregulation of axon guidance proteins causes disease will help the development of therapeutic strategies for neurological disorders.
PMID: 25769423 [PubMed - indexed for MEDLINE]
[New aspects in the field of epilepsy].
Nervenarzt. 2014 Aug;85(8):955-64
Authors: Rosenow F, Klein KM, Strzelczyk A, Hamer HM, Menzler K, Bauer S, Knake S
Regarding epilepsy several new developments can be reported. The International League Against Epilepsy (ILAE) has suggested a new definition of epilepsy, for the first time including a definition of epilepsy resolution. Progress in the diagnosis relates to new genetic findings, improvements in magnetic resonance imaging (MRI) and the increasing use of stereo electroencephalograms (sEEG). Regarding treatment there are new clinically relevant data on the pathophysiology and prevention of sudden unexpected death in epilepsy (SUDEP). Zonisamide has been approved by the European Medicines Agency (EMA) for monotherapy in adults with focal seizures and combination therapy in children aged ≥ 6 years. Retigabin and perampanel have been approved but are currently taken off the market in Germany (only) because the Gemeinsamer Bundesausschuss (GBA, Joint Federal Committee) did not find any additional therapeutic value as compared to lamotrigine due to a lack of data. A decision regarding a new application for perampanel is pending. Regarding surgical treatment novel ablation techniques (e.g. stereotactic radiofrequency and laser ablation as well as focussed ultrasound ablation) and brain stimulation paradigms are under investigation. Experimental studies, generously supported by the European Union (EU) and the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) are focusing on (opto-)genetic (e.g. using lentoviral transfection), epigenetic (e.g. micro-RNA-related) approaches and on the investigation of neuronal micronetworks.
PMID: 25022893 [PubMed - indexed for MEDLINE]
MicroRNA and epilepsy: profiling, functions and potential clinical applications.
Curr Opin Neurol. 2014 Apr;27(2):199-205
Authors: Henshall DC
PURPOSE OF REVIEW: This review provides a synthesis of recent profiling studies investigating microRNA (miRNA) changes in experimental and human epilepsy, and outlines mechanistic, therapeutic and diagnostic potentials of this research area for clinical practice.
RECENT FINDINGS: A series of studies in experimental and human epilepsy have undertaken large-scale expression profiling of miRNAs, key regulatory molecules in cells controlling protein levels. Levels of over 100 different miRNAs were found to either increase or decrease in the hippocampus, of which more than 20 were identified in more than one study, including higher levels of miR-23a, miR-34a, miR-132 and miR-146a. Altered levels of enzymes involved in miRNA biogenesis and function, including Dicer and Argonaute 2, have also been found in epileptic brain tissue. Functional studies using oligonucleotide-based inhibitors support roles for miRNAs in the control of cell death, synaptic structure, inflammation and the immune response. Finally, data show brain injuries that precipitate epilepsy generate unique miRNA profiles in biofluids.
SUMMARY: miRNA represents a potentially important mechanism controlling protein levels in epilepsy. As such, miRNAs might be targeted to prevent or disrupt epilepsy as well as serve as diagnostic biomarkers of epileptogenesis.
PMID: 24553459 [PubMed - indexed for MEDLINE]