ALS Genetics, Mechanisms, and Therapeutics: Where Are We Now?

Rita Mejzini, Loren L. Flynn, Ianthe L. Pitout, Sue Fletcher, Steve D. Wilton, P. Anthony Akkari

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

The scientific landscape surrounding amyotrophic lateral sclerosis (ALS) continues to shift as the number of genes associated with the disease risk and pathogenesis, and the cellular processes involved, continues to grow. Despite decades of intense research and over 50 potentially causative or disease-modifying genes identified, etiology remains unexplained and treatment options remain limited for the majority of ALS patients. Various factors have contributed to the slow progress in understanding and developing therapeutics for this disease. Here, we review the genetic basis of ALS, highlighting factors that have contributed to the elusiveness of genetic heritability. The most commonly mutated ALS-linked genes are reviewed with an emphasis on disease-causing mechanisms. The cellular processes involved in ALS pathogenesis are discussed, with evidence implicating their involvement in ALS summarized. Past and present therapeutic strategies and the benefits and limitations of the model systems available to ALS researchers are discussed with future directions for research that may lead to effective treatment strategies outlined.

Original languageEnglish
Article number1310
JournalFrontiers in Neuroscience
Volume13
DOIs
Publication statusPublished - 6 Dec 2019

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@article{36b619f77e834f4097fce1e80c9b7c79,
title = "ALS Genetics, Mechanisms, and Therapeutics: Where Are We Now?",
abstract = "The scientific landscape surrounding amyotrophic lateral sclerosis (ALS) continues to shift as the number of genes associated with the disease risk and pathogenesis, and the cellular processes involved, continues to grow. Despite decades of intense research and over 50 potentially causative or disease-modifying genes identified, etiology remains unexplained and treatment options remain limited for the majority of ALS patients. Various factors have contributed to the slow progress in understanding and developing therapeutics for this disease. Here, we review the genetic basis of ALS, highlighting factors that have contributed to the elusiveness of genetic heritability. The most commonly mutated ALS-linked genes are reviewed with an emphasis on disease-causing mechanisms. The cellular processes involved in ALS pathogenesis are discussed, with evidence implicating their involvement in ALS summarized. Past and present therapeutic strategies and the benefits and limitations of the model systems available to ALS researchers are discussed with future directions for research that may lead to effective treatment strategies outlined.",
keywords = "amyotrophic lateral sclerosis, cell models, disease mechanisms, FUS, missing heritability, TDP-43, therapeutics",
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ALS Genetics, Mechanisms, and Therapeutics : Where Are We Now? / Mejzini, Rita; Flynn, Loren L.; Pitout, Ianthe L.; Fletcher, Sue; Wilton, Steve D.; Akkari, P. Anthony.

In: Frontiers in Neuroscience, Vol. 13, 1310, 06.12.2019.

Research output: Contribution to journalReview article

TY - JOUR

T1 - ALS Genetics, Mechanisms, and Therapeutics

T2 - Where Are We Now?

AU - Mejzini, Rita

AU - Flynn, Loren L.

AU - Pitout, Ianthe L.

AU - Fletcher, Sue

AU - Wilton, Steve D.

AU - Akkari, P. Anthony

PY - 2019/12/6

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N2 - The scientific landscape surrounding amyotrophic lateral sclerosis (ALS) continues to shift as the number of genes associated with the disease risk and pathogenesis, and the cellular processes involved, continues to grow. Despite decades of intense research and over 50 potentially causative or disease-modifying genes identified, etiology remains unexplained and treatment options remain limited for the majority of ALS patients. Various factors have contributed to the slow progress in understanding and developing therapeutics for this disease. Here, we review the genetic basis of ALS, highlighting factors that have contributed to the elusiveness of genetic heritability. The most commonly mutated ALS-linked genes are reviewed with an emphasis on disease-causing mechanisms. The cellular processes involved in ALS pathogenesis are discussed, with evidence implicating their involvement in ALS summarized. Past and present therapeutic strategies and the benefits and limitations of the model systems available to ALS researchers are discussed with future directions for research that may lead to effective treatment strategies outlined.

AB - The scientific landscape surrounding amyotrophic lateral sclerosis (ALS) continues to shift as the number of genes associated with the disease risk and pathogenesis, and the cellular processes involved, continues to grow. Despite decades of intense research and over 50 potentially causative or disease-modifying genes identified, etiology remains unexplained and treatment options remain limited for the majority of ALS patients. Various factors have contributed to the slow progress in understanding and developing therapeutics for this disease. Here, we review the genetic basis of ALS, highlighting factors that have contributed to the elusiveness of genetic heritability. The most commonly mutated ALS-linked genes are reviewed with an emphasis on disease-causing mechanisms. The cellular processes involved in ALS pathogenesis are discussed, with evidence implicating their involvement in ALS summarized. Past and present therapeutic strategies and the benefits and limitations of the model systems available to ALS researchers are discussed with future directions for research that may lead to effective treatment strategies outlined.

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KW - cell models

KW - disease mechanisms

KW - FUS

KW - missing heritability

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