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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doaj-ed915efdd5d74487b17d63edfc3103d62020-11-25T00:05:05ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992017-08-011010.3389/fnmol.2017.00263285028Autophagy Dysregulation in ALS: When Protein Aggregates Get Out of HandNandini Ramesh0Nandini Ramesh1Udai Bhan Pandey2Udai Bhan Pandey3Udai Bhan Pandey4Department of Human Genetics, University of Pittsburgh Graduate School of Public HealthPittsburgh, PA, United StatesDivision of Child Neurology, Department of Pediatrics, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical CenterPittsburgh, PA, United StatesDepartment of Human Genetics, University of Pittsburgh Graduate School of Public HealthPittsburgh, PA, United StatesDivision of Child Neurology, Department of Pediatrics, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical CenterPittsburgh, PA, United StatesDepartment of Neurology, University of Pittsburgh School of MedicinePittsburgh, PA, United StatesAmyotrophic 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 in vitro and in vivo 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.http://journal.frontiersin.org/article/10.3389/fnmol.2017.00263/fullALSautophagySOD1TDP-43FUSC9orf72 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nandini Ramesh Nandini Ramesh Udai Bhan Pandey Udai Bhan Pandey Udai Bhan Pandey |
spellingShingle |
Nandini Ramesh Nandini Ramesh Udai Bhan Pandey Udai Bhan Pandey Udai Bhan Pandey Autophagy Dysregulation in ALS: When Protein Aggregates Get Out of Hand Frontiers in Molecular Neuroscience ALS autophagy SOD1 TDP-43 FUS C9orf72 |
author_facet |
Nandini Ramesh Nandini Ramesh Udai Bhan Pandey Udai Bhan Pandey Udai Bhan Pandey |
author_sort |
Nandini Ramesh |
title |
Autophagy Dysregulation in ALS: When Protein Aggregates Get Out of Hand |
title_short |
Autophagy Dysregulation in ALS: When Protein Aggregates Get Out of Hand |
title_full |
Autophagy Dysregulation in ALS: When Protein Aggregates Get Out of Hand |
title_fullStr |
Autophagy Dysregulation in ALS: When Protein Aggregates Get Out of Hand |
title_full_unstemmed |
Autophagy Dysregulation in ALS: When Protein Aggregates Get Out of Hand |
title_sort |
autophagy dysregulation in als: when protein aggregates get out of hand |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Molecular Neuroscience |
issn |
1662-5099 |
publishDate |
2017-08-01 |
description |
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 in vitro and in vivo 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. |
topic |
ALS autophagy SOD1 TDP-43 FUS C9orf72 |
url |
http://journal.frontiersin.org/article/10.3389/fnmol.2017.00263/full |
work_keys_str_mv |
AT nandiniramesh autophagydysregulationinalswhenproteinaggregatesgetoutofhand AT nandiniramesh autophagydysregulationinalswhenproteinaggregatesgetoutofhand AT udaibhanpandey autophagydysregulationinalswhenproteinaggregatesgetoutofhand AT udaibhanpandey autophagydysregulationinalswhenproteinaggregatesgetoutofhand AT udaibhanpandey autophagydysregulationinalswhenproteinaggregatesgetoutofhand |
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1725426332010020864 |