Autophagy Dysregulation in ALS: When Protein Aggregates Get Out of Hand

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that results from the loss of upper and lower motor neurons. One of the key pathological hallmarks in diseased neurons is the mislocalization of disease-associated proteins and the formation of cytoplasmic aggregates of these protei...

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Bibliographic Details
Published in:Frontiers in molecular neuroscience 2017-08, Vol.10, p.263-263
Main Authors: Ramesh, Nandini, Pandey, Udai Bhan
Format: Article
Language:English
Subjects:
Aggregates
ALS
Amyotrophic lateral sclerosis
Autophagy
C9orf72
Cell death
Cellular stress response
FUS
Homeostasis
Motor neurons
Mutation
Neurodegeneration
Neurodegenerative diseases
Neurons
Neuroscience
Organelles
Pathology
Patients
Phagocytosis
Proteins
Quality control
SOD1
Spinal cord
TDP-43
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Summary:Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that results from the loss of upper and lower motor neurons. One of the key pathological hallmarks in diseased neurons is the mislocalization of disease-associated proteins and the formation of cytoplasmic aggregates of these proteins and their interactors due to defective protein quality control. This apparent imbalance in the cellular protein homeostasis could be a crucial factor in causing motor neuron death in the later stages of the disease in patients. Autophagy is a major protein degradation pathway that is involved in the clearance of protein aggregates and damaged organelles. Abnormalities in autophagy have been observed in numerous neurodegenerative disorders, including ALS. In this review, we discuss the contribution of autophagy dysfunction in various and models of ALS. Furthermore, we examine the crosstalk between autophagy and other cellular stresses implicated in ALS pathogenesis and the therapeutic implications of regulating autophagy in ALS.
ISSN:1662-5099
1662-5099
DOI:10.3389/fnmol.2017.00263