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1.
Front Aging Neurosci ; 11: 313, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31780922

RESUMO

Neurodegenerative diseases are disorders that are characterized by a progressive decline of motor and/or cognitive functions caused by the selective degeneration and loss of neurons within the central nervous system. The most common neurodegenerative diseases are Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Neurons have high energy demands, and dysregulation of mitochondrial quality and function is an important cause of neuronal degeneration. Mitochondrial quality control plays an important role in maintaining mitochondrial integrity and ensuring normal mitochondrial function; thus, defects in mitochondrial quality control are also significant causes of neurodegenerative diseases. The mitochondrial deacetylase SIRT3 has been found to have a large effect on mitochondrial function. Recent studies have also shown that SIRT3 has a role in mitochondrial quality control, including in the refolding or degradation of misfolded/unfolded proteins, mitochondrial dynamics, mitophagy, and mitochondrial biogenesis, all of which are affected in neurodegenerative diseases.

2.
Neurochem Res ; 44(9): 2031-2043, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31410709

RESUMO

As one of the major cell organelles responsible for ATP production, it is important that neurons maintain mitochondria with structural and functional integrity; this is especially true for neurons with high metabolic requirements. When mitochondrial damage occurs, mitochondria are able to maintain a steady state of functioning through molecular and organellar quality control, thus ensuring neuronal function. And when mitochondrial quality control (MQC) fails, mitochondria mediate apoptosis. An apparently key molecule in MQC is the transcriptional coactivator peroxisome proliferator activated receptor γ coactivator-1α (PGC-1α). Recent findings have demonstrated that upregulation of PGC-1α expression in neurons can modulate MQC to prevent mitochondrial dysfunction in certain in vivo and in vitro aging or neurodegenerative encephalopathy models, such as Huntington's disease, Alzheimer's disease, and Parkinson's disease. Because mitochondrial function and quality control disorders are the basis of pathogenesis in almost all neurodegenerative diseases (NDDs), the role of PGC-1α may make it a viable entry point for the treatment of such diseases. This review focuses on multi-level MQC in neurons, as well as the regulation of MQC by PGC-1α in these major NDDs.


Assuntos
Doença de Alzheimer/fisiopatologia , Doença de Huntington/fisiopatologia , Mitocôndrias/fisiologia , Doença de Parkinson/fisiopatologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/fisiologia , Animais , Humanos , Neurônios/fisiologia , Biogênese de Organelas
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