Brás José, Gibbons Elizabeth, Guerreiro Rita
Center for Neurodegenerative Science, Van Andel Institute, 333 Bostwick Ave. N.E., Grand Rapids, MI, 49503-2518, USA.
Division of Psychiatry and Behavioral Medicine, Michigan State University College of Human Medicine, Grand Rapids, MI, USA.
Acta Neuropathol. 2021 Apr;141(4):471-490. doi: 10.1007/s00401-020-02202-1. Epub 2020 Aug 1.
The SNCA locus currently has an indisputable role in Parkinson's disease and other synucleinopathies. The role of genetic variability in the other members of the synuclein family (SNCB and SNCG) in disease is far less clear. In this review, we critically assess the pathogenicity, main characteristics, and roles of genetic variants in these genes reported to be causative of synucleinopathies. We also summarize the different association signals identified in the SNCA locus that have been associated with risk for disease. We take a bird's eye view of the variability currently reported in the general population for the three genes and use these data to infer on the potential relationship between each of the genes and human disease.
目前，α-突触核蛋白（SNCA）基因座在帕金森病和其他突触核蛋白病中具有无可争议的作用。而突触核蛋白家族其他成员（β-突触核蛋白[SNCB]和γ-突触核蛋白[SNCG]）的基因变异在疾病中的作用则远不明确。在本综述中，我们严格评估了据报道可导致突触核蛋白病的这些基因中基因变异的致病性、主要特征及作用。我们还总结了在SNCA基因座中已确定的与疾病风险相关的不同关联信号。我们全面审视了目前在普通人群中报道的这三个基因的变异性，并利用这些数据来推断每个基因与人类疾病之间的潜在关系。
