TY - JOUR
T1 - Modulating α-synuclein propagation and decomposition
T2 - Implications in Parkinson's disease therapy
AU - Li, Beining
AU - Xiao, Xue
AU - Bi, Mingxia
AU - Jiao, Qian
AU - Chen, Xi
AU - Yan, Chunling
AU - Du, Xixun
AU - Jiang, Hong
N1 - Publisher Copyright:
© 2024 Elsevier B.V.
PY - 2024/7
Y1 - 2024/7
N2 - α-Synuclein (α-Syn) is closely related to the pathogenesis of Parkinson's disease (PD). Under pathological conditions, the conformation of α-syn changes and different forms of α-syn lead to neurotoxicity. According to Braak stages, α-syn can propagate in different brain regions, inducing neurodegeneration and corresponding clinical manifestations through abnormal aggregation of Lewy bodies (LBs) and lewy axons in different types of neurons in PD. So far, PD lacks early diagnosis biomarkers, and treatments are mainly targeted at some clinical symptoms. There is no effective therapy to delay the progression of PD. This review first summarized the role of α-syn in physiological and pathological states, and the relationship between α-syn and PD. Then, we focused on the origin, secretion, aggregation, propagation and degradation of α-syn as well as the important regulatory factors in these processes systematically. Finally, we reviewed some potential drug candidates for alleviating the abnormal aggregation of α-syn in order to provide valuable targets for the treatment of PD to cope with the occurrence and progression of this disease.
AB - α-Synuclein (α-Syn) is closely related to the pathogenesis of Parkinson's disease (PD). Under pathological conditions, the conformation of α-syn changes and different forms of α-syn lead to neurotoxicity. According to Braak stages, α-syn can propagate in different brain regions, inducing neurodegeneration and corresponding clinical manifestations through abnormal aggregation of Lewy bodies (LBs) and lewy axons in different types of neurons in PD. So far, PD lacks early diagnosis biomarkers, and treatments are mainly targeted at some clinical symptoms. There is no effective therapy to delay the progression of PD. This review first summarized the role of α-syn in physiological and pathological states, and the relationship between α-syn and PD. Then, we focused on the origin, secretion, aggregation, propagation and degradation of α-syn as well as the important regulatory factors in these processes systematically. Finally, we reviewed some potential drug candidates for alleviating the abnormal aggregation of α-syn in order to provide valuable targets for the treatment of PD to cope with the occurrence and progression of this disease.
KW - Parkinson's disease
KW - decomposition
KW - propagation
KW - α-synuclein fibrils
KW - α-synuclein oligomers
UR - https://www.scopus.com/pages/publications/85192722487
U2 - 10.1016/j.arr.2024.102319
DO - 10.1016/j.arr.2024.102319
M3 - 文献综述
C2 - 38719160
AN - SCOPUS:85192722487
SN - 1568-1637
VL - 98
JO - Ageing Research Reviews
JF - Ageing Research Reviews
M1 - 102319
ER -