黑质
自噬
铁蛋白
致密部
细胞生物学
帕金森病
背景(考古学)
生物
α-突触核蛋白
神经退行性变
线粒体
多巴胺能
蛋白质聚集
神经科学
多巴胺
生物化学
疾病
医学
病理
细胞凋亡
古生物学
作者
Matthew K. Boag,Angus Roberts,Vladimir N. Uversky,Linlin Ma,Des R. Richardson,Dean L. Pountney
摘要
A major hallmark of Parkinson's disease (PD) is the fatal destruction of dopaminergic neurons within the substantia nigra pars compacta. This event is preceded by the formation of Lewy bodies, which are cytoplasmic inclusions composed of α-synuclein protein aggregates. A triad contribution of α-synuclein aggregation, iron accumulation, and mitochondrial dysfunction plague nigral neurons, yet the events underlying iron accumulation are poorly understood. Elevated intracellular iron concentrations up-regulate ferritin expression, an iron storage protein that provides cytoprotection against redox stress. The lysosomal degradation pathway, autophagy, can release iron from ferritin stores to facilitate its trafficking in a process termed ferritinophagy. Aggregated α-synuclein inhibits SNARE protein complexes and destabilizes microtubules to halt vesicular trafficking systems, including that of autophagy effectively. The scope of this review is to describe the physiological and pathological relationship between iron regulation and α-synuclein, providing a detailed understanding of iron metabolism within nigral neurons. The underlying mechanisms of autophagy and ferritinophagy are explored in the context of PD, identifying potential therapeutic targets for future investigation.
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