| First Author | McLean JR | Year | 2012 |
| Journal | Mol Cell Neurosci | Volume | 49 |
| Issue | 2 | Pages | 230-9 |
| PubMed ID | 22155155 | Mgi Jnum | J:191533 |
| Mgi Id | MGI:5462014 | Doi | 10.1016/j.mcn.2011.11.006 |
| Citation | McLean JR, et al. (2012) Transcript expression levels of full-length alpha-synuclein and its three alternatively spliced variants in Parkinson's disease brain regions and in a transgenic mouse model of alpha-synuclein overexpression. Mol Cell Neurosci 49(2):230-9 |
| abstractText | Alternative splicing is a complex post-transcriptional process that can be regulated by cis-acting elements located within genomic non-coding regions. Recent studies have identified that polymorphic variations in non-coding regions of the alpha-synuclein gene (SNCA) locus are associated with an increased risk for developing Parkinson's disease (PD). The underlying mechanism(s) for this susceptibility may involve changes in alpha-synuclein mRNA expression and alternative splicing. As a first step towards understanding the biology of alpha-synuclein splice variants in PD, we characterized the levels of the full-length SNCA-140 mRNA transcript and SNCA-126, -112, and -98 alternatively spliced variants in different neuronal regions from PD patients or transgenic mice overexpressing human alpha-synuclein (ASO). In human post-mortem tissue, alpha-synuclein spliced transcripts were expressed in a region-specific manner in the cortex, substantia nigra, and cerebellum. We observed increased nigral SNCA-140 and SNCA-126 transcript levels in PD patients when compared to neurologically unaffected cases. Human alpha-synuclein splicing changes were also found to occur in a region-specific manner in ASO mice. Here, SNCA-126, -112, and -98 transcript levels did not increase proportionally with SNCA-140 levels, or parallel the region-specific mouse transcript ratios seen in wild-type (WT) littermates. While most transcripts were elevated in ASO mice when compared to WT mice, the most prominent increase was found in the ventral midbrain of 15-month-old ASO mice. These results demonstrate region-specific human alpha-synuclein transcript level abnormalities in PD patients and in a transgenic mouse model of alpha-synucleinopathy. This study is relevant to understanding the normal, adaptive, or pathological role(s) of alpha-synuclein splice variants. |
