The Role of BDNF Signaling in ALS.
The molecular basis for motor nerve dysfunction and death in Amyotrophic Lateral Sclerosis (ALS) is still poorly understood. Here, we hypothesize that the “trophic” factor brain-derived neurotrophic factor (BDNF), that is normally produced by muscles and other tissues to keep the nerve functioning is instead modified to an immature, toxic form, which leads to disruption of the nerve-muscle connection and ultimately nerve cell death. Such immature factors have been found to cause damage in the brain following injury, or during nerve cell death for example in Alzheimer’s disease, but whether they contribute to the progression of ALS is unknown. The central objective of this proposal is to elucidate the potential role of these factors in motor nerve dysfunction. We will characterize BDNF and proBDNF's levels during disease progression in a well-described mouse model of ALS, and investigate their impact on the nerve-muscle connection as well as on the survival of motor nerve cells. Total Internal Reflection Fluorescence (TIRF) microscopy and spinning disk confocal will be used to track the dynamics and spatiotemporal localization of pro/mature BDNF's receptors, TrkB and p75NTR in order to elucidate their mechanism of action. Successful completion of this study may open new avenues for future ALS therapeutic strategies, and novel understanding of the relationship between ligand-receptor localization and function.
Participant in the delegation of Tel Aviv University student and faculty in the 2014 “XIN conference” at Tsinghua University, Beijing.
Participant in the 2015 Neurotrophic factor Gordon research conference at Salve Regina University, Newport, RI.
Gluska S, Chein M, Rotem N, Perlson E ( 2015) – Tracking Quantum-Dot labeled neurotropic factors transport along primary neuronal axons in compartmental microfluidic chambers - Methods in Cell Biology.
Gershoni-Emek N, Mazza A, Chein M, Gradus T, Xiang X, Li K W, Sharon R and Perlson E (2015) - Proteomic Analysis of Dynein interactors in Synaptosomes reveals a role for the RNA-binding Protein Staufen1 in Amyotrophic Lateral Sclerosis – Molecular and cellular proteomics.
Gershoni-Emek N, Chein M, Gluska S, Perlson E (2015) New insight into the mechanism of motor neuron survival and synapse maintenance – International Review of Cell & Molecular Biology.
Gluska S, Zahavi EE, Chein M, Gradus T, Bauer A, Finke S, and Perlson E (2014)- Rabies Virus Hijacks and Accelerates the p75NTR Retrograde Axonal Transport Machinery – PloS Pathogens.
2014 “XIN conference” travel grant and scholarship.
Research Categories: Cellular/molecular neuroscience