Macroautophagy and Mitophagy in Neurodegenerative Disorders: Focus on Therapeutic Interventions

Macroautophagy, a quality control mechanism, is an evolutionarily conserved pathway of lysosomal degradation of protein aggregates, pathogens, and damaged organelles. As part of its vital homeostatic role, macroautophagy deregulation is associated with various human disorders, including neurodegener...

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Bibliographic Details
Published in:Biomedicines 2021-11, Vol.9 (11), p.1625
Main Authors: Magalhães, João Duarte, Fão, Lígia, Vilaça, Rita, Cardoso, Sandra Morais, Rego, Ana Cristina
Format: Article
Language:English
Subjects:
Autophagy
Biosynthesis
Cell division
Etiology
Homeostasis
Huntingtin
Kinases
Lysosomes
Membranes
Metabolites
Mitochondria
Mitophagy
mitophagy mitochondrial dysfunction
mutant proteins
Neurodegeneration
Neurodegenerative diseases
neurodegenerative disorders
Organelles
Phagocytosis
Phosphorylation
Protein folding
Proteins
Quality control
Regulation
Review
Synuclein
Tau protein
Therapeutic applications
therapeutic strategies
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Summary:Macroautophagy, a quality control mechanism, is an evolutionarily conserved pathway of lysosomal degradation of protein aggregates, pathogens, and damaged organelles. As part of its vital homeostatic role, macroautophagy deregulation is associated with various human disorders, including neurodegenerative diseases. There are several lines of evidence that associate protein misfolding and mitochondrial dysfunction in the etiology of Alzheimer’s, Parkinson’s, and Huntington’s diseases. Macroautophagy has been implicated in the degradation of different protein aggregates such as Aβ, tau, alpha-synuclein (α-syn), and mutant huntingtin (mHtt) and in the clearance of dysfunctional mitochondria. Taking these into consideration, targeting autophagy might represent an effective therapeutic strategy to eliminate protein aggregates and to improve mitochondrial function in these disorders. The present review describes our current understanding on the role of macroautophagy in neurodegenerative disorders and focuses on possible strategies for its therapeutic modulation.
ISSN:2227-9059
2227-9059
DOI:10.3390/biomedicines9111625