| First Author | Ruiz R | Year | 2014 |
| Journal | Neuropharmacology | Volume | 76 Pt A |
| Pages | 106-17 | PubMed ID | 24036317 |
| Mgi Jnum | J:202023 | Mgi Id | MGI:5516514 |
| Doi | 10.1016/j.neuropharm.2013.08.032 | Citation | Ruiz R, et al. (2014) alpha-Synuclein A30P decreases neurodegeneration and increases synaptic vesicle release probability in CSPalpha-null mice. Neuropharmacology 76 Pt A:106-17 |
| abstractText | alpha-Synuclein and Cysteine-string protein-alpha (CSPalpha) are presynaptic proteins that participate in the maintenance of synaptic function. Mutations or overexpression of the wild type form of alpha-synuclein have been related to Parkinson's disease, and CSPalpha mutations cause one type of neuronal ceroid lipofuscinosis. Both are adult-onset neurodegenerative diseases characterized by neuronal protein aggregations. Strikingly, while in mouse the lack of CSPalpha produces defective neurotransmission and neurodegeneration of motor terminals, blindness and early lethality, the moderate overexpression of wild-type alpha-synuclein fully rescues the CSPalpha-null phenotype. Contrarily, the overexpression of the mutated human alpha-synuclein A30P (alpha-synuclein(hA30P)) has much less effect in CSPalpha KO mice. To explore how the A30P mutation affects the neuroprotective function of alpha-synuclein we investigated synaptic structure and neurotransmission in motor nerve terminals of wild-type and CSPalpha-null mice transgenic for alpha-synuclein(hA30P). We found that although alpha-synuclein(hA30P) did not fully prevent neurodegeneration, it significantly improved synaptic organization and function in CSPalpha-null mice by enhancing quantal content, release probability, synaptic vesicle content, active zone number, postsynaptic area, and microtubule appearance. These results demonstrate that alpha-synuclein(hA30P) is able to ameliorate synapse degeneration, despite its apparent lack of functionality and its long-term pathogenic effects in neurons. These findings may help to understand better the dual function of alpha-synuclein regarding neurodegeneration. This article is part of the Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'. |
