帕金
生物
帕金森病
突变
遗传学
泛素连接酶
品脱1
线粒体
表型
细胞生物学
异质性
泛素
基因
粒体自噬
帕金森病
内科学
医学
自噬
疾病
细胞凋亡
作者
Martina Sevegnani,Adriano Lama,Francesco Girardi,Michael W. Hess,Maria Paulina Castelo,Irene Pichler,Stefano Biressi,Giovanni Piccoli
标识
DOI:10.1016/j.bbadis.2024.167302
摘要
Recessive mutations in the Parkin gene (PRKN) are the most common cause of young-onset inherited parkinsonism. Parkin is a multifunctional E3 ubiquitin ligase that plays a variety of roles in the cell including the degradation of proteins and the maintenance of mitochondrial homeostasis, integrity, and biogenesis. In 2001, the R275W mutation in the PRKN gene was identified in two unrelated families with a multigenerational history of postural tremor, dystonia and parkinsonism. Drosophila models of Parkin R275W showed selective and progressive degeneration of dopaminergic neuronal clusters, mitochondrial abnormalities, and prominent climbing defects. In the Prkn mouse orthologue, the amino acid R274 corresponds to human R275. Here we described an age-related motor impairment and a muscle phenotype in R274W +/+ mice. In vitro, Parkin R274W mutation correlates with abnormal myoblast differentiation, mitochondrial defects, and alteration in mitochondrial mRNA and protein levels. Our data suggest that the Parkin R274W mutation may impact mitochondrial physiology and eventually myoblast proliferation and differentiation.
科研通智能强力驱动
Strongly Powered by AbleSci AI