Presynaptic neurodegeneration: CSP-alpha/DNAJC5 at the synaptic vesicle cycle and beyond
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-a (CSP-a...
| Autores: | , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2018 |
| País: | España |
| Institución: | Universidad de Sevilla (US) |
| Repositorio: | idUS. Depósito de Investigación de la Universidad de Sevilla |
| OAI Identifier: | oai:idus.us.es:11441/167750 |
| Acceso en línea: | https://hdl.handle.net/11441/167750 https://doi.org/10.1016/j.cophys.2018.06.001 |
| Access Level: | acceso abierto |
| Palabra clave: | Synaptic vesicle Synaptic degeneration CSP-alpha DNAJC5 Lipofuscinosis Amyotrophic lateral sclerosis Alzheimer disease Prionlike propagation |
| Sumario: | 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-a (CSP-a/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-a/DNAJC5 nerve terminals suffer from activity-dependent neurodegeration. In humans CSP-a/DNAJC5 has been linked to severe neurodegeneration in neuronal ceroid lipofuscinosis. Recent studies involve CSP a/DNAJC5 in the clearance of misfolded proteins. In any case, the detailed mechanisms by which CSP-a/DNAJC5 prevent synaptic degeneration are not fully understood yet |
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