Olfactory deficit and gastrointestinal dysfunction precede motor abnormalities in alpha- Synuclein G51D knock- in mice

• 成果类型: Article
• 署名作者: Kim, Youngdoo; McInnes, Joseph; Kim, Jiyoen; Liang, Yan Hong Wei; Veeraragavan, Surabi; Garza, Alexandra Rae; Belfort, Benjamin David Webst; Arenkiel, Benjamin; Samaco, Rodney; Zoghbi, Huda Yahya
• 署名单位: Baylor College of Medicine; Baylor College of Medicine; Baylor College Medical Hospital; Baylor College of Medicine; Baylor College of Medicine; Baylor College of Medicine; Baylor College of Medicine; Howard Hughes Medical Institute
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-14633
• DOI: 10.1073/pnas.2406479121
• 发表日期: 2024-09-24
• 关键词: parkinson-like neurodegeneration; alzheimers-disease; substantia-nigra; wild-type; Mutation; phosphorylation; accumulation; degeneration; aggregation; modulation

摘要

Parkinson's disease (PD) is typically a sporadic late- onset disorder, which has made it difficult to model in mice. Several transgenic mouse models bearing mutations in SNCA, which encodes alpha- Synuclein (alpha- Syn), have been made, but these lines do not express SNCA in a physiologically accurate spatiotemporal pattern, which limits the ability of the mice to recapitulate the features of human PD. Here, we generated knock- in mice bearing the G51D SNCA mutation. After establishing that their motor symptoms begin at 9 mo of age, we then sought earlier pathologies. We assessed the phosphorylation at Serine 129 of alpha- Syn in different tissues and detected phospho- alpha-Syn in the olfactory bulb and enteric nervous system at 3 mo of age. Olfactory deficit and thus parallel the progression of human PD and will enable us to study PD pathogenesis and test future therapies.