期刊
DISEASE MODELS & MECHANISMS
卷 6, 期 2, 页码 424-433出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dmm.009761
关键词
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资金
- Joseph and Kathleen Bryan Alzheimer's Disease Research Center, DUMC, Durham, NC, USA (NIA) [5P50 AG05128]
- Fondazione Cariparma
- Italian Ministry of Education, University and Research (MIUR)
- MIUR [prot. 2007945BZN]
- Associazione Italiana Ricerca sul Cancro (AIRC) [IG9378]
- Associazione Italiana per la Lotta al Neuroblastoma (Genoa, Italy)
- Italian Ministry of Education, University and Research (MIUR-FIRB) [RBAP11HSZS]
Recent studies indicated that sortilin-related receptor 1 (SORL1) is a risk gene for late-onset Alzheimer's disease (AD), although its role in the aetiology and/or progression of this disorder is not fully understood. Here, we report the finding of a non-coding (nc) RNA (hereafter referred to as 51A) that maps in antisense configuration to intron 1 of the SORL1 gene. 51A expression drives a splicing shift of SORL1 from the synthesis of the canonical long protein variant A to an alternatively spliced protein form. This process, resulting in a decreased synthesis of SORL1 variant A, is associated with impaired processing of amyloid precursor protein (APP), leading to increased A beta formation. Interestingly, we found that 51A is expressed in human brains, being frequently upregulated in cerebral cortices from individuals with Alzheimer's disease. Altogether, these findings document a novel ncRNA-dependent regulatory pathway that might have relevant implications in neurodegeneration.
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