Alpha-synuclein immunoreactivity of huntingtin polyglutamine aggregates in striatum and cortex of Huntington's disease patients and transgenic mouse models

Vinod Charles, Eva Mezey, P (Hemachandra) Reddy, Anindya Dehejia, Theresa A. Young, Mihail H. Polymeropoulos, Michael J. Brownstein, Danilo A. Tagle

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Polyglutamine expansions in proteins are implicated in at least eight inherited neurodegenerative disorders, including Huntington's disease. These mutant proteins can form aggregates within the nucleus and processes of neurons possibly due to misfolding of the proteins. Polyglutamine aggregates are ubiquitinated and sequester molecular chaperone proteins and proteasome components. To investigate other protein components of polyglutamine aggregates, cerebral cortex and striata from patients with Huntington's disease and full-length cDNA transgenic mouse models for this disease were examined immunohistochemically for α-synuclein reactivity. Our findings demonstrate that α-synuclein can be used as a marker for huntingtin polyglutamine aggregates in both human and mice. Moreover in the HD transgenic mice, the intensity of immunoreactivity increases with age. The significance of recruitment of α-synuclein into huntingtin aggregates and its translocation away from the synapses remains to be determined. We propose that aberrant interaction of mutant huntingtin with other proteins, including α-synuclein, may influence disease progression. Copyright (C) 2000 Elsevier Science Ireland Ltd.

Original languageEnglish (US)
Pages (from-to)29-32
Number of pages4
JournalNeuroscience Letters
Volume289
Issue number1
DOIs
StatePublished - Jul 28 2000
Externally publishedYes

Fingerprint

alpha-Synuclein
Synucleins
Huntington Disease
Transgenic Mice
Proteins
Molecular Chaperones
Proteasome Endopeptidase Complex
Mutant Proteins
Neurodegenerative Diseases
Cerebral Cortex
Synapses
Disease Progression
Complementary DNA
polyglutamine
Neurons

Keywords

  • α-Synuclein
  • Cerebral cortex
  • Huntingtin
  • Huntington's disease
  • Immunohistochemistry
  • Parkinson's disease
  • Striatum
  • Transgenic mice

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Alpha-synuclein immunoreactivity of huntingtin polyglutamine aggregates in striatum and cortex of Huntington's disease patients and transgenic mouse models. / Charles, Vinod; Mezey, Eva; Reddy, P (Hemachandra); Dehejia, Anindya; Young, Theresa A.; Polymeropoulos, Mihail H.; Brownstein, Michael J.; Tagle, Danilo A.

In: Neuroscience Letters, Vol. 289, No. 1, 28.07.2000, p. 29-32.

Research output: Contribution to journalArticle

Charles, Vinod ; Mezey, Eva ; Reddy, P (Hemachandra) ; Dehejia, Anindya ; Young, Theresa A. ; Polymeropoulos, Mihail H. ; Brownstein, Michael J. ; Tagle, Danilo A. / Alpha-synuclein immunoreactivity of huntingtin polyglutamine aggregates in striatum and cortex of Huntington's disease patients and transgenic mouse models. In: Neuroscience Letters. 2000 ; Vol. 289, No. 1. pp. 29-32.
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