Presynaptic neurodegeneration: CSP-α/DNAJC5 at the synaptic vesicle cycle and beyond

• Published in: Current opinion in physiology Vol. 4; pp. 65 - 69
• Main Authors: Valenzuela-Villatoro, Marina, García-Junco-Clemente, Pablo, Nieto-González, José L, Fernández-Chacón, Rafael
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.08.2018
• ISSN: 2468-8673; 2468-8673
• DOI: 10.1016/j.cophys.2018.06.001

•Synapses need local mechanisms to maintain long-term proteostasis.•CSP-α /DNAJC5 essential for synaptic vesicle cycling and presynaptic maintenance.•CSP-α/DNAJC5 mutations cause neurodegeneration in humans.•CSP-α /DNAJC5 might promote the clearance of misfolded proteins. Presynaptic terminals need reliable mechanisms to maintain the molecular homeostasis of hundreds of thousands of crowded protein molecules. How do synapses, located far away from the soma and active for many decades, face alterations due to activity-dependent stress? Cysteine string protein-α (CSP-α/DNAJC5) is a synaptic vesicle co-chaperone required for the stability of the SNARE complex, that mediates neurotransmitter release, and for the normal recycling of synaptic vesicles. Without CSP-α/DNAJC5 nerve terminals suffer from activity-dependent neurodegeration. In humans CSP-α/DNAJC5 has been linked to severe neurodegeneration in neuronal ceroid lipofuscinosis. Recent studies involve CSP-α/DNAJC5 in the clearance of misfolded proteins. In any case, the detailed mechanisms by which CSP-α/DNAJC5 prevent synaptic degeneration are not fully understood yet.