Targeting Sirtuin-1 in Huntington's disease: Rationale and current status

Research output: Contribution to journalArticle

Abstract

Huntington's disease (HD) is an autosomal dominant hereditary disease caused by a trinucleotide repeat mutation in the huntingtin gene that results in an increased number of glutamine residues in the N terminus of huntingtin protein. Mutant huntingtin leads to progressive impairment of motor function, cognitive dysfunction, and neuropsychiatric disturbance. There are no disease-modifying treatments available. During the past decade, sirtuin-1 (SIRT1) has been the focus of intense investigation and discussion because it regulates longevity in multiple organisms and has shown beneficial effects in a variety of models of neurodegenerative disorders. Studies in different animal models provide convincing evidence that SIRT1 protects neurons in mouse models of HD as well as in Caenorhabditis elegans, although controversial results were reported in a fly model. Indeed, many connections exist between the deacetylation function of SIRT1 and its role in neuroprotection. As a result, pharmacological interventions targeting SIRT1 might become promising strategies to combat HD. This review summarizes recent progress in SIRT1 research, with a focus on the specificity of this protein as a potential therapeutic target for HD, as well as existing challenges for developing SIRT1 modulators for clinical use.

Original languageEnglish (US)
Pages (from-to)345-352
Number of pages8
JournalCNS Drugs
Volume27
Issue number5
DOIs
StatePublished - May 2013

Fingerprint

Sirtuin 1
Huntington Disease
Trinucleotide Repeats
Inborn Genetic Diseases
Caenorhabditis elegans
Glutamine
Diptera
Neurodegenerative Diseases
Animal Models
Pharmacology
Neurons
Mutation
Research

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Psychiatry and Mental health
  • Clinical Neurology

Cite this

Targeting Sirtuin-1 in Huntington's disease : Rationale and current status. / Duan, Wenzhen.

In: CNS Drugs, Vol. 27, No. 5, 05.2013, p. 345-352.

Research output: Contribution to journalArticle

@article{e20c188d53844f4dab9a104f4115ce66,
title = "Targeting Sirtuin-1 in Huntington's disease: Rationale and current status",
abstract = "Huntington's disease (HD) is an autosomal dominant hereditary disease caused by a trinucleotide repeat mutation in the huntingtin gene that results in an increased number of glutamine residues in the N terminus of huntingtin protein. Mutant huntingtin leads to progressive impairment of motor function, cognitive dysfunction, and neuropsychiatric disturbance. There are no disease-modifying treatments available. During the past decade, sirtuin-1 (SIRT1) has been the focus of intense investigation and discussion because it regulates longevity in multiple organisms and has shown beneficial effects in a variety of models of neurodegenerative disorders. Studies in different animal models provide convincing evidence that SIRT1 protects neurons in mouse models of HD as well as in Caenorhabditis elegans, although controversial results were reported in a fly model. Indeed, many connections exist between the deacetylation function of SIRT1 and its role in neuroprotection. As a result, pharmacological interventions targeting SIRT1 might become promising strategies to combat HD. This review summarizes recent progress in SIRT1 research, with a focus on the specificity of this protein as a potential therapeutic target for HD, as well as existing challenges for developing SIRT1 modulators for clinical use.",
author = "Wenzhen Duan",
year = "2013",
month = "5",
doi = "10.1007/s40263-013-0055-0",
language = "English (US)",
volume = "27",
pages = "345--352",
journal = "CNS Drugs",
issn = "1172-7047",
publisher = "Adis International Ltd",
number = "5",

}

TY - JOUR

T1 - Targeting Sirtuin-1 in Huntington's disease

T2 - Rationale and current status

AU - Duan, Wenzhen

PY - 2013/5

Y1 - 2013/5

N2 - Huntington's disease (HD) is an autosomal dominant hereditary disease caused by a trinucleotide repeat mutation in the huntingtin gene that results in an increased number of glutamine residues in the N terminus of huntingtin protein. Mutant huntingtin leads to progressive impairment of motor function, cognitive dysfunction, and neuropsychiatric disturbance. There are no disease-modifying treatments available. During the past decade, sirtuin-1 (SIRT1) has been the focus of intense investigation and discussion because it regulates longevity in multiple organisms and has shown beneficial effects in a variety of models of neurodegenerative disorders. Studies in different animal models provide convincing evidence that SIRT1 protects neurons in mouse models of HD as well as in Caenorhabditis elegans, although controversial results were reported in a fly model. Indeed, many connections exist between the deacetylation function of SIRT1 and its role in neuroprotection. As a result, pharmacological interventions targeting SIRT1 might become promising strategies to combat HD. This review summarizes recent progress in SIRT1 research, with a focus on the specificity of this protein as a potential therapeutic target for HD, as well as existing challenges for developing SIRT1 modulators for clinical use.

AB - Huntington's disease (HD) is an autosomal dominant hereditary disease caused by a trinucleotide repeat mutation in the huntingtin gene that results in an increased number of glutamine residues in the N terminus of huntingtin protein. Mutant huntingtin leads to progressive impairment of motor function, cognitive dysfunction, and neuropsychiatric disturbance. There are no disease-modifying treatments available. During the past decade, sirtuin-1 (SIRT1) has been the focus of intense investigation and discussion because it regulates longevity in multiple organisms and has shown beneficial effects in a variety of models of neurodegenerative disorders. Studies in different animal models provide convincing evidence that SIRT1 protects neurons in mouse models of HD as well as in Caenorhabditis elegans, although controversial results were reported in a fly model. Indeed, many connections exist between the deacetylation function of SIRT1 and its role in neuroprotection. As a result, pharmacological interventions targeting SIRT1 might become promising strategies to combat HD. This review summarizes recent progress in SIRT1 research, with a focus on the specificity of this protein as a potential therapeutic target for HD, as well as existing challenges for developing SIRT1 modulators for clinical use.

UR - http://www.scopus.com/inward/record.url?scp=84878573777&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878573777&partnerID=8YFLogxK

U2 - 10.1007/s40263-013-0055-0

DO - 10.1007/s40263-013-0055-0

M3 - Article

C2 - 23549885

AN - SCOPUS:84878573777

VL - 27

SP - 345

EP - 352

JO - CNS Drugs

JF - CNS Drugs

SN - 1172-7047

IS - 5

ER -