4.6 Article

Pathological Relevance of Post-Translationally Modified Alpha-Synuclein (pSer87, pSer129, nTyr39) in Idiopathic Parkinson's Disease and Multiple System Atrophy

期刊

CELLS
卷 11, 期 5, 页码 -

出版社

MDPI
DOI: 10.3390/cells11050906

关键词

alpha-synuclein; post-translational modifications; Parkinson's disease; multiple system atrophy; Lewy bodies; Lewy neurites; glial cytoplasmic inclusions; phosphorylation; nitration; immunohistochemistry

资金

  1. Reta Lila Weston Trust Fund
  2. British Neuropathological Society
  3. EPFL
  4. Michael J Fox foundation
  5. Cayman Island Government

向作者/读者索取更多资源

The predominant post-translational modifications of alpha-synuclein in the pathological process of idiopathic Parkinson's disease and multiple system atrophy were found to be phosphorylation and nitration, with phosphorylated alpha-synuclein being the earliest and most abundant form. These findings may have implications for the development of novel biomarkers and therapeutic approaches.
Aggregated alpha-synuclein (alpha-synuclein) is the main component of Lewy bodies (LBs), Lewy neurites (LNs), and glial cytoplasmic inclusions (GCIs), which are pathological hallmarks of idiopathic Parkinson's disease (IPD) and multiple system atrophy (MSA). Initiating factors that culminate in forming LBs/LNs/GCIs remain elusive. Several species of alpha-synuclein exist, including phosphorylated and nitrated forms. It is unclear which alpha-synuclein post-translational modifications (PTMs) appear within aggregates throughout disease pathology. Herein we aimed to establish the predominant alpha-synuclein PTMs in postmortem IPD and MSA pathology using immunohistochemistry. We examined the patterns of three alpha-synuclein PTMs (pS87, pS129, nY39) simultaneously in pathology-affected regions of 15 IPD cases, 5 MSA cases, and 6 neurologically normal controls. All antibodies recognized LBs, LNs, and GCIs, albeit to a variable extent. pS129 alpha-synuclein antibody was particularly immunopositive for LNs and synaptic dot-like structures, followed by nY39 alpha-synuclein antibody. GCIs, neuronal inclusions, and small threads were positive for nY39 alpha-synuclein in MSA. Quantification of the LB scores revealed that pS129 alpha-synuclein was the dominant and earliest alpha-synuclein PTM, followed by nY39 alpha-synuclein, while lower amounts of pSer87 alpha-synuclein appeared later in disease progression in PD. These results may have implications for novel biomarker and therapeutic developments.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据