Pharmacological promotion of inclusion formation

A therapeutic approach for Huntington's and Parkinson's diseases

Ruth A. Bodner, Tiago Fleming Outeiro, Stephen Altmann, Michele M. Maxwell, Stephanie H. Cho, Bradley T. Hyman, Pamela J McLean, Anne B. Young, David E. Housman, Aleksey G. Kazantsev

Research output: Contribution to journalArticle

208 Citations (Scopus)

Abstract

Misfolded proteins accumulate in many neurodegenerative diseases, including huntingtin in Huntington's disease and α-synuclein in Parkinson's disease. The disease-causing proteins can take various conformations and are prone to aggregate and form larger cytoplasmic or nuclear inclusions. One approach to the development of therapeutic intervention for these diseases has been to identify chemical compounds that reduce the size or number of inclusions. We have, however, identified a compound that promotes inclusion formation in cellular models of both Huntington's disease and Parkinson's disease. Of particular interest, this compound prevents huntingtin-mediated proteasome dysfunction and reduces α-synuclein-mediated toxicity. These results demonstrate that compounds that increase inclusion formation may actually lessen cellular pathology in both Huntington's and Parkinson's diseases, suggesting a therapeutic approach for neurodegenerative diseases caused by protein misfolding.

Original languageEnglish (US)
Pages (from-to)4246-4251
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number11
DOIs
StatePublished - Mar 14 2006
Externally publishedYes

Fingerprint

Huntington Disease
Synucleins
Parkinson Disease
Pharmacology
Neurodegenerative Diseases
Intranuclear Inclusion Bodies
Proteins
Inclusion Bodies
Proteasome Endopeptidase Complex
Therapeutics
Pathology

Keywords

  • Misfolded proteins
  • Neurodegenerative disease

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Pharmacological promotion of inclusion formation : A therapeutic approach for Huntington's and Parkinson's diseases. / Bodner, Ruth A.; Outeiro, Tiago Fleming; Altmann, Stephen; Maxwell, Michele M.; Cho, Stephanie H.; Hyman, Bradley T.; McLean, Pamela J; Young, Anne B.; Housman, David E.; Kazantsev, Aleksey G.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 103, No. 11, 14.03.2006, p. 4246-4251.

Research output: Contribution to journalArticle

Bodner, Ruth A. ; Outeiro, Tiago Fleming ; Altmann, Stephen ; Maxwell, Michele M. ; Cho, Stephanie H. ; Hyman, Bradley T. ; McLean, Pamela J ; Young, Anne B. ; Housman, David E. ; Kazantsev, Aleksey G. / Pharmacological promotion of inclusion formation : A therapeutic approach for Huntington's and Parkinson's diseases. In: Proceedings of the National Academy of Sciences of the United States of America. 2006 ; Vol. 103, No. 11. pp. 4246-4251.
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