Protein folding alterations in amyotrophic lateral sclerosis

Research output: Contribution to journalReview articleResearchpeer-review

Abstract

Protein misfolding leads to the formation of aggregated proteins and protein inclusions, which are associated with synaptic loss and neuronal death in neurodegenerative diseases. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that targets motor neurons in the brain, brainstem and spinal cord. Several proteins misfold and are associated either genetically or pathologically in ALS, including superoxide dismutase 1 (SOD1), Tar DNA binding protein-43 (TDP-43), Ubiquilin-2, p62, VCP, and dipeptide repeat proteins produced by unconventional repeat associated non-ATG translation of the repeat expansion in C9ORF72. Chaperone proteins, including heat shock proteins (Hsp׳s) and the protein disulphide isomerase (PDI) family, assist in protein folding and therefore can prevent protein misfolding, and have been implicated as being protective in ALS. In this review we provide an overview of the current literature regarding the molecular mechanisms of protein misfolding and aggregation in ALS, and the role of chaperones as potential targets for therapeutic intervention. This article is part of a Special Issue entitled SI:ER stress.

LanguageEnglish
Pages633-649
Number of pages17
JournalBrain Research
Volume1648
DOIs
Publication statusPublished - 1 Oct 2016

Fingerprint

Protein Folding
Amyotrophic Lateral Sclerosis
Proteins
Neurodegenerative Diseases
Protein Disulfide-Isomerases
Tars
Dipeptides
DNA-Binding Proteins
Motor Neurons
Heat-Shock Proteins
Brain Stem
Spinal Cord
Brain

Keywords

  • Amyotrophic lateral sclerosis
  • C9ORF72
  • Disulphide bonds
  • ER stress
  • FUS
  • Protein disulphide isomerase (PDI)
  • Protein misfolding
  • Superoxide dismutase 1 (SOD1)
  • TDP-43

Cite this

@article{173df76444de42439b547e0566fd5054,
title = "Protein folding alterations in amyotrophic lateral sclerosis",
abstract = "Protein misfolding leads to the formation of aggregated proteins and protein inclusions, which are associated with synaptic loss and neuronal death in neurodegenerative diseases. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that targets motor neurons in the brain, brainstem and spinal cord. Several proteins misfold and are associated either genetically or pathologically in ALS, including superoxide dismutase 1 (SOD1), Tar DNA binding protein-43 (TDP-43), Ubiquilin-2, p62, VCP, and dipeptide repeat proteins produced by unconventional repeat associated non-ATG translation of the repeat expansion in C9ORF72. Chaperone proteins, including heat shock proteins (Hsp׳s) and the protein disulphide isomerase (PDI) family, assist in protein folding and therefore can prevent protein misfolding, and have been implicated as being protective in ALS. In this review we provide an overview of the current literature regarding the molecular mechanisms of protein misfolding and aggregation in ALS, and the role of chaperones as potential targets for therapeutic intervention. This article is part of a Special Issue entitled SI:ER stress.",
keywords = "Amyotrophic lateral sclerosis, C9ORF72, Disulphide bonds, ER stress, FUS, Protein disulphide isomerase (PDI), Protein misfolding, Superoxide dismutase 1 (SOD1), TDP-43",
author = "Sonam Parakh and Atkin, {Julie D.}",
year = "2016",
month = "10",
day = "1",
doi = "10.1016/j.brainres.2016.04.010",
language = "English",
volume = "1648",
pages = "633--649",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",

}

Protein folding alterations in amyotrophic lateral sclerosis. / Parakh, Sonam; Atkin, Julie D.

In: Brain Research, Vol. 1648, 01.10.2016, p. 633-649.

Research output: Contribution to journalReview articleResearchpeer-review

TY - JOUR

T1 - Protein folding alterations in amyotrophic lateral sclerosis

AU - Parakh, Sonam

AU - Atkin, Julie D.

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Protein misfolding leads to the formation of aggregated proteins and protein inclusions, which are associated with synaptic loss and neuronal death in neurodegenerative diseases. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that targets motor neurons in the brain, brainstem and spinal cord. Several proteins misfold and are associated either genetically or pathologically in ALS, including superoxide dismutase 1 (SOD1), Tar DNA binding protein-43 (TDP-43), Ubiquilin-2, p62, VCP, and dipeptide repeat proteins produced by unconventional repeat associated non-ATG translation of the repeat expansion in C9ORF72. Chaperone proteins, including heat shock proteins (Hsp׳s) and the protein disulphide isomerase (PDI) family, assist in protein folding and therefore can prevent protein misfolding, and have been implicated as being protective in ALS. In this review we provide an overview of the current literature regarding the molecular mechanisms of protein misfolding and aggregation in ALS, and the role of chaperones as potential targets for therapeutic intervention. This article is part of a Special Issue entitled SI:ER stress.

AB - Protein misfolding leads to the formation of aggregated proteins and protein inclusions, which are associated with synaptic loss and neuronal death in neurodegenerative diseases. Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that targets motor neurons in the brain, brainstem and spinal cord. Several proteins misfold and are associated either genetically or pathologically in ALS, including superoxide dismutase 1 (SOD1), Tar DNA binding protein-43 (TDP-43), Ubiquilin-2, p62, VCP, and dipeptide repeat proteins produced by unconventional repeat associated non-ATG translation of the repeat expansion in C9ORF72. Chaperone proteins, including heat shock proteins (Hsp׳s) and the protein disulphide isomerase (PDI) family, assist in protein folding and therefore can prevent protein misfolding, and have been implicated as being protective in ALS. In this review we provide an overview of the current literature regarding the molecular mechanisms of protein misfolding and aggregation in ALS, and the role of chaperones as potential targets for therapeutic intervention. This article is part of a Special Issue entitled SI:ER stress.

KW - Amyotrophic lateral sclerosis

KW - C9ORF72

KW - Disulphide bonds

KW - ER stress

KW - FUS

KW - Protein disulphide isomerase (PDI)

KW - Protein misfolding

KW - Superoxide dismutase 1 (SOD1)

KW - TDP-43

UR - http://www.scopus.com/inward/record.url?scp=84975746049&partnerID=8YFLogxK

U2 - 10.1016/j.brainres.2016.04.010

DO - 10.1016/j.brainres.2016.04.010

M3 - Review article

VL - 1648

SP - 633

EP - 649

JO - Brain Research

T2 - Brain Research

JF - Brain Research

SN - 0006-8993

ER -