Redox regulation in amyotrophic lateral sclerosis

Sonam Parakh, Damian M. Spencer, Mark A. Halloran, Kai Y. Soo, Julie D. Atkin

Research output: Contribution to journalReview articleResearchpeer-review

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that results from the death of upper and lower motor neurons. Due to a lack of effective treatment, it is imperative to understand the underlying mechanisms and processes involved in disease progression. Regulations in cellular reduction/oxidation (redox) processes are being increasingly implicated in disease. Here we discuss the possible involvement of redox dysregulation in the pathophysiology of ALS, either as a cause of cellular abnormalities or a consequence. We focus on its possible role in oxidative stress, protein misfolding, glutamate excitotoxicity, lipid peroxidation and cholesterol esterification, mitochondrial dysfunction, impaired axonal transport and neurofilament aggregation, autophagic stress, and endoplasmic reticulum (ER) stress. We also speculate that an ER chaperone protein disulphide isomerase (PDI) could play a key role in this dysregulation. PDI is essential for normal protein folding by oxidation and reduction of disulphide bonds, and hence any disruption to this process may have consequences for motor neurons. Addressing the mechanism underlying redox regulation and dysregulation may therefore help to unravel the molecular mechanism involved in ALS.

LanguageEnglish
Article number408681
Pages1-12
Number of pages12
JournalOxidative Medicine and Cellular Longevity
Volume2013
DOIs
Publication statusPublished - 2013
Externally publishedYes

Fingerprint

Amyotrophic Lateral Sclerosis
Oxidation-Reduction
Protein Disulfide-Isomerases
Motor Neurons
Oxidation
Neurons
Axonal Transport
Endoplasmic Reticulum Stress
Intermediate Filaments
Esterification
Protein Folding
Neurodegenerative diseases
Heat-Shock Proteins
Protein folding
Endoplasmic Reticulum
Disulfides
Neurodegenerative Diseases
Lipid Peroxidation
Oxidative stress
Disease Progression

Cite this

Parakh, Sonam ; Spencer, Damian M. ; Halloran, Mark A. ; Soo, Kai Y. ; Atkin, Julie D. / Redox regulation in amyotrophic lateral sclerosis. In: Oxidative Medicine and Cellular Longevity. 2013 ; Vol. 2013. pp. 1-12.
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Redox regulation in amyotrophic lateral sclerosis. / Parakh, Sonam; Spencer, Damian M.; Halloran, Mark A.; Soo, Kai Y.; Atkin, Julie D.

In: Oxidative Medicine and Cellular Longevity, Vol. 2013, 408681, 2013, p. 1-12.

Research output: Contribution to journalReview articleResearchpeer-review

TY - JOUR

T1 - Redox regulation in amyotrophic lateral sclerosis

AU - Parakh, Sonam

AU - Spencer, Damian M.

AU - Halloran, Mark A.

AU - Soo, Kai Y.

AU - Atkin, Julie D.

PY - 2013

Y1 - 2013

N2 - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that results from the death of upper and lower motor neurons. Due to a lack of effective treatment, it is imperative to understand the underlying mechanisms and processes involved in disease progression. Regulations in cellular reduction/oxidation (redox) processes are being increasingly implicated in disease. Here we discuss the possible involvement of redox dysregulation in the pathophysiology of ALS, either as a cause of cellular abnormalities or a consequence. We focus on its possible role in oxidative stress, protein misfolding, glutamate excitotoxicity, lipid peroxidation and cholesterol esterification, mitochondrial dysfunction, impaired axonal transport and neurofilament aggregation, autophagic stress, and endoplasmic reticulum (ER) stress. We also speculate that an ER chaperone protein disulphide isomerase (PDI) could play a key role in this dysregulation. PDI is essential for normal protein folding by oxidation and reduction of disulphide bonds, and hence any disruption to this process may have consequences for motor neurons. Addressing the mechanism underlying redox regulation and dysregulation may therefore help to unravel the molecular mechanism involved in ALS.

AB - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that results from the death of upper and lower motor neurons. Due to a lack of effective treatment, it is imperative to understand the underlying mechanisms and processes involved in disease progression. Regulations in cellular reduction/oxidation (redox) processes are being increasingly implicated in disease. Here we discuss the possible involvement of redox dysregulation in the pathophysiology of ALS, either as a cause of cellular abnormalities or a consequence. We focus on its possible role in oxidative stress, protein misfolding, glutamate excitotoxicity, lipid peroxidation and cholesterol esterification, mitochondrial dysfunction, impaired axonal transport and neurofilament aggregation, autophagic stress, and endoplasmic reticulum (ER) stress. We also speculate that an ER chaperone protein disulphide isomerase (PDI) could play a key role in this dysregulation. PDI is essential for normal protein folding by oxidation and reduction of disulphide bonds, and hence any disruption to this process may have consequences for motor neurons. Addressing the mechanism underlying redox regulation and dysregulation may therefore help to unravel the molecular mechanism involved in ALS.

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