Possible Alterations in β-Synuclein, the Non-Amyloidogenic Homologue of α-Synuclein, during Progression of Sporadic α-Synucleinopathies

International Journal of Molecular Sciences

Masayo Fujita¹  Akio Sekigawa²  Kazunari Sekiyama²  Yoshiki Takamatsu² 

[1] Division of Sensory and Motor Systems, Tokyo Metropolitan Institute of Medical Science, 2-1-6 Kamikitazawa Setagaya-ku Tokyo 156-0057, Japan;

关键词: α-synucleinopathies;    α-synuclein;    β-synuclein;    dementia with Lewy bodies;    toxic gain of function;   

DOI  :  10.3390/ijms130911584

来源: mdpi

【 摘 要 】

α-Synucleinopathies are neurodegenerative disorders that are characterized by progressive decline of motor and non-motor dysfunctions. α-Synuclein (αS) has been shown to play a causative role in neurodegeneration, but the pathogenic mechanisms are still unclear. Thus, there are no radical therapies that can halt or reverse the disease’s progression. β-Synuclein (βS), the non-amyloidogenic homologue of αS, ameliorates the neurodegeneration phenotype of αS in transgenic (tg) mouse models, as well as in cell free and cell culture systems, which suggests that βS might be a negative regulator of neurodegeneration caused by αS, and that “loss of function” of βS might be involved in progression of α-synucleinopathies. Alternatively, it is possible that “toxic gain of function” of wild type βS occurs during the pathogenesis of sporadic α-synucleinopathies, since tg mice expressing dementia with Lewy bodies-linked P123H βS develop progressive neurodegeneration phenotypes, such as axonal pathology and dementia. In this short review, we emphasize the aspects of “toxic gain of function” of wild type βS during the pathogenesis of sporadic α-synucleinopathies.

【 授权许可】

CC BY   
© 2012 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.