Understanding the Multiple Role of Mitochondria in Parkinson's Disease and Related Disorders: Lesson From Genetics and Protein-Interaction Network

被引:45
|
作者
Nicoletti, Valentina [1 ]
Palermo, Giovanni [1 ]
Del Prete, Eleonora [1 ]
Mancuso, Michelangelo [1 ]
Ceravolo, Roberto [1 ]
机构
[1] Univ Pisa, Dept Clin & Expt Med, Neurol Unit, Pisa, Italy
来源
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY | 2021年 / 9卷
关键词
Parkinson’ s disease; atypical parkinsonism; Huntington disease; mitochondrial dysfunction; neurodegenerative diseases; Pink1; parkin pathway; alpha-synuclein; PROGRESSIVE SUPRANUCLEAR PALSY; HUNTINGTONS-DISEASE; RESPIRATORY-CHAIN; ALPHA-SYNUCLEIN; MUTANT HUNTINGTIN; SKELETAL-MUSCLE; AXONAL-TRANSPORT; OXIDATIVE STRESS; DNA DELETIONS; COMPLEX-I;
D O I
10.3389/fcell.2021.636506
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
As neurons are highly energy-demanding cell, increasing evidence suggests that mitochondria play a large role in several age-related neurodegenerative diseases. Synaptic damage and mitochondrial dysfunction have been associated with early events in the pathogenesis of major neurodegenerative diseases, including Parkinson's disease, atypical parkinsonisms, and Huntington disease. Disruption of mitochondrial structure and dynamic is linked to increased levels of reactive oxygen species production, abnormal intracellular calcium levels, and reduced mitochondrial ATP production. However, recent research has uncovered a much more complex involvement of mitochondria in such disorders than has previously been appreciated, and a remarkable number of genes and proteins that contribute to the neurodegeneration cascade interact with mitochondria or affect mitochondrial function. In this review, we aim to summarize and discuss the deep interconnections between mitochondrial dysfunction and basal ganglia disorders, with an emphasis into the molecular triggers to the disease process. Understanding the regulation of mitochondrial pathways may be beneficial in finding pharmacological or non-pharmacological interventions to delay the onset of neurodegenerative diseases.
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页数:20
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