Targeted proteolytic products of τ and α-synuclein in neurodegeneration.
Targeted proteolytic products of τ and α-synuclein in neurodegeneration.
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DOI：
10.1042/ebc20210028
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发表时间：
2021-12-22
影响因子：
6.4
通讯作者：
Giasson BI
中科院分区：
文献类型：
--
作者：
Xia Y;Lloyd GM;Giasson BI
包含τ或α-突触核蛋白（αSyn）的CNS病理性包涵体定义了一系列神经退行性疾病，并且这些疾病通常可以同时存在于同一个体中。这两种蛋白质的聚集明显与神经变性相关，并且每种蛋白质的有害性质进一步得到导致疾病的每种基因（分别为MAPT和SNCA）突变的支持。大多数散发性神经退行性疾病的起始事件仍不清楚，但越来越多的证据表明τ和αSyn的异常蛋白水解裂解导致可能具有毒性和/或引发可通过朊病毒样机制进一步传播的聚集的产物。这些裂解产物中的一些的积累可以进一步加强蛋白质聚集传递的进展，并导致它们在外周生物流体如脑脊液（CSF）和血液中的积累。未来开发新的工具来检测外周生物液中特异性τ和αSyn异常裂解产物可能是有用的生物标志物，并且更好地了解独特蛋白水解活性的作用可以产生治疗干预。
CNS pathological inclusions comprising τ or α-synuclein (αSyn) define a spectrum of neurodegenerative diseases, and these can often present concurrently in the same individuals. The aggregation of both proteins is clearly associated with neurodegeneration and the deleterious properties of each protein is further supported by mutations in each gene (MAPT and SNCA, respectively) resulting in disease. The initiating events in most sporadic neurodegenerative diseases are still unclear but growing evidence suggests that the aberrant proteolytic cleavage of τ and αSyn results in products that can be toxic and/or initiate aggregation that can further spread by a prion-like mechanism. The accumulation of some of these cleavage products can further potentiate the progression of protein aggregation transmission and lead to their accumulation in peripheral biofluids such as cerebrospinal fluid (CSF) and blood. The future development of new tools to detect specific τ and αSyn abnormal cleavage products in peripheral biofluids could be useful biomarkers and better understand of the role of unique proteolytic activities could yield therapeutic interventions.