Institut de Neuropatologia, Servei Anatomia Patològica, IDIBELL-Hospital Universitari de Bellvitge, Hospitalet de LLobregat, CIBERNED, Instituto Carlos III, Barcelona, Spain.
Neuroscience. 2012 Jan 3;200:106-19. doi: 10.1016/j.neuroscience.2011.10.042. Epub 2011 Oct 29.
α-synuclein is a key protein in Lewy body diseases (LBDs) and a major component of Lewy bodies and related aberrant cytoplasmic and neuritic inclusions. Regional differences in α-synuclein have been associated with selective neuronal vulnerability to Lewy pathology. Furthermore, phosphorylation at serine 129 (Ser129) and α-synuclein truncation have been considered crucial in the pathogenesis of Lewy inclusions. The present study shows consistent reduction in α-synuclein protein expression levels in the human substantia nigra and nucleus basalis of Meynert compared with other brain regions independently of age and pathology. Phosphorylated α-synuclein at Ser129 is naturally increased in these same regions, thus inversely related with the total amount of α-synuclein. In contrast, truncated α-synuclein is naturally observed in control and diseased brains and correlating with the total amount of α-synuclein. Several truncated variants have been identified where some of these variants are truncated at the C-terminal domain, whereas others are truncated at the N-terminal domain, and all are present in cases with and without Lewy pathology. Although accumulation of truncated α-synuclein variants and phosphorylated α-synuclein occurs in Lewy bodies, α-synuclein phosphorylation and truncation can be considered constitutive in control and diseased brains.
α-突触核蛋白是路易体疾病（LBDs）的关键蛋白，也是路易体和相关异常细胞质和神经突包含物的主要成分。α-突触核蛋白的区域差异与路易病病理学对选择性神经元易感性有关。此外，丝氨酸 129（Ser129）的磷酸化和α-突触核蛋白截断被认为在路易包涵体的发病机制中至关重要。本研究显示，与其他脑区相比，人类黑质和梅内特基底核中的α-突触核蛋白表达水平一致降低，与年龄和病理学无关。在这些相同的区域，磷酸化的α-突触核蛋白 Ser129 自然增加，因此与α-突触核蛋白的总量呈负相关。相比之下，截断的α-突触核蛋白在对照和患病脑中自然存在，并与α-突触核蛋白的总量相关。已经鉴定出几种截断的变体，其中一些变体在 C 末端结构域截断，而另一些在 N 末端结构域截断，所有这些变体都存在于有或没有路易病病理学的病例中。尽管截断的α-突触核蛋白变体和磷酸化的α-突触核蛋白在路易体中积累，但α-突触核蛋白的磷酸化和截断可以被认为是对照和患病脑中的组成性。
