title: Cysteine string protein (CSP) and its role in preventing neurodegeneration.
abstract: Cysteine string protein (CSP) is a member of the DnaJ/Hsp40 family of co-chaperones that localises to neuronal synaptic vesicles. Its name derives from the possession of a string of 12-15 cysteine residues, palmitoylation of which is required for targeting to post-Golgi membranes. The DnaJ domain of CSP enables it to bind client proteins and recruit Hsc70 chaperones, thereby contributing to the maintenance of protein folding in the presynaptic compartment. Mutation of CSP in flies, worms and mice reduces lifespan and causes synaptic dysfunction and neurodegeneration. Furthermore, recent studies have revealed that the neurodegenerative disease, adult onset neuronal ceroid lipofuscinosis, is caused by mutations in the human CSPα-encoding DNAJC5 gene. Accumulating evidence suggests that the major mechanism by which CSP prevents neurodegeneration is by maintaining the conformation of SNAP-25, thereby facilitating its entry into the membrane-fusing SNARE complex. In this review, we focus on the role of CSP in preventing neurodegeneration and discuss how recent studies of this universal neuroprotective chaperone are being translated into potential novel therapeutics for neurodegenerative diseases.
authors: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Crown St., Liverpool L69 3BX, UK.
authors: Robert D
authors: RD
authors: Burgoyne
authors: Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Crown St., Liverpool L69 3BX, UK. Electronic address: amorgan@liverpool.ac.uk.
authors: Alan
authors: A
authors: Morgan
mesh_terms: D000818:Animals; D050956:HSP40 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control*; D017510:Protein Folding; D017434:Protein Structure, Tertiary
chemical_list: D050956:HSP40 Heat-Shock Proteins; D008565:Membrane Proteins; C088460:cysteine string protein
keywords: Adult onset neuronal ceroid lipofuscinosis; Alzheimer's disease; DNAJC5; Resveratrol; SNAP-25; SNAREs