Mechanisms underlying neurodegeneration in Huntington disease: applications to novel disease-modifying therapies

Christopher A. Ross; Martin Kronenbuerger; Wenzhen Duan; Russell L. Margolis

doi:10.1016/B978-0-12-801893-4.00002-X

Mechanisms underlying neurodegeneration in Huntington disease: applications to novel disease-modifying therapies

Christopher A. Ross, Martin Kronenbuerger, Wenzhen Duan, Russell L. Margolis

School of Medicine

Research output: Chapter in Book/Report/Conference proceeding › Chapter

5 Scopus citations

Abstract

The CAG repeat expansion mutation that causes Huntington Disease (HD) was discovered more than 20 years ago, yet no treatment has yet been developed to stop the relentless course of the disease. Nonetheless, substantial progress has been made in understanding HD pathogenesis. We review insights that have been gleaned from HD genetics, metabolism, and pathology; HD mouse and cell models; the structure, function and post-translational modification of normal and mutant huntingtin (htt) protein; gene expression profiles in HD cells and tissue; the neurotoxicy of mutant htt RNA; and the expression of an antisense transcript from the HD locus. We conclude that rationale therapeutics for HD is within sight, though many questions remain to be answered.

Original language	English (US)
Title of host publication	Handbook of Clinical Neurology
Publisher	Elsevier B.V.
Pages	15-28
Number of pages	14
DOIs	https://doi.org/10.1016/B978-0-12-801893-4.00002-X
State	Published - 2017

Publication series

Name	Handbook of Clinical Neurology
Volume	144
ISSN (Print)	0072-9752
ISSN (Electronic)	2212-4152

Keywords

Huntingtin
aggregation
antisense
gene transcription
inclusion

ASJC Scopus subject areas

Neurology
Clinical Neurology

Access to Document

10.1016/B978-0-12-801893-4.00002-X

Cite this

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abstract = "The CAG repeat expansion mutation that causes Huntington Disease (HD) was discovered more than 20 years ago, yet no treatment has yet been developed to stop the relentless course of the disease. Nonetheless, substantial progress has been made in understanding HD pathogenesis. We review insights that have been gleaned from HD genetics, metabolism, and pathology; HD mouse and cell models; the structure, function and post-translational modification of normal and mutant huntingtin (htt) protein; gene expression profiles in HD cells and tissue; the neurotoxicy of mutant htt RNA; and the expression of an antisense transcript from the HD locus. We conclude that rationale therapeutics for HD is within sight, though many questions remain to be answered.",

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AU - Duan, Wenzhen

AU - Margolis, Russell L.

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AB - The CAG repeat expansion mutation that causes Huntington Disease (HD) was discovered more than 20 years ago, yet no treatment has yet been developed to stop the relentless course of the disease. Nonetheless, substantial progress has been made in understanding HD pathogenesis. We review insights that have been gleaned from HD genetics, metabolism, and pathology; HD mouse and cell models; the structure, function and post-translational modification of normal and mutant huntingtin (htt) protein; gene expression profiles in HD cells and tissue; the neurotoxicy of mutant htt RNA; and the expression of an antisense transcript from the HD locus. We conclude that rationale therapeutics for HD is within sight, though many questions remain to be answered.

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KW - inclusion

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Mechanisms underlying neurodegeneration in Huntington disease: applications to novel disease-modifying therapies

Abstract

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Keywords

ASJC Scopus subject areas

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