| First Author | Kim T | Year | 2016 |
| Journal | J Neurosci | Volume | 36 |
| Issue | 26 | Pages | 7055-65 |
| PubMed ID | 27358461 | Mgi Jnum | J:234644 |
| Mgi Id | MGI:5790526 | Doi | 10.1523/JNEUROSCI.1241-16.2016 |
| Citation | Kim T, et al. (2016) Poststroke Induction of alpha-Synuclein Mediates Ischemic Brain Damage. J Neurosci 36(26):7055-65 |
| abstractText | alpha-Synuclein (alpha-Syn), one of the most abundant proteins in the CNS, is known to be a major player in the neurodegeneration observed in Parkinson's disease. We currently report that transient focal ischemia upregulates alpha-Syn protein expression and nuclear translocation in neurons of the adult rodent brain. We further show that knockdown or knock-out of alpha-Syn significantly decreases the infarction and promotes better neurological recovery in rodents subjected to focal ischemia. Furthermore, alpha-Syn knockdown significantly reduced postischemic induction of phospho-Drp1, 3-nitrotyrosine, cleaved caspase-3, and LC-3 II/I, indicating its role in modulating mitochondrial fragmentation, oxidative stress, apoptosis, and autophagy, which are known to mediate poststroke neuronal death. Transient focal ischemia also significantly upregulated serine-129 (S129) phosphorylation (palpha-Syn) of alpha-Syn and nuclear translocation of palpha-Syn. Furthermore, knock-out mice that lack PLK2 (the predominant kinase that mediates S129 phosphorylation) showed better functional recovery and smaller infarcts when subjected to transient focal ischemia, indicating a detrimental role of S129 phosphorylation of alpha-Syn. In conclusion, our studies indicate that alpha-Syn is a potential therapeutic target to minimize poststroke brain damage. SIGNIFICANCE STATEMENT: Abnormal aggregation of alpha-synuclein (alpha-Syn) has been known to cause Parkinson's disease and other chronic synucleinopathies. However, even though alpha-Syn is linked to pathophysiological mechanisms similar to those that produce acute neurodenegerative disorders, such as stroke, the role of alpha-Syn in such disorder is not clear. We presently studied whether alpha-Syn mediates poststroke brain damage and more importantly whether preventing alpha-Syn expression is neuroprotective and leads to better physiological and functional outcome after stroke. Our study indicates that alpha-Syn is a potential therapeutic target for stroke therapy. |
