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

Polyglutamine expansions in proteins are implicated in at least eight inher ited neurodegenerative disorders, including Huntington's disease. These mut ant proteins can form aggregates with in the nucleus and processes of neuro ns possibly due to misfolding of the proteins. Polyglutamine aggregates are ubiquitinated and sequester molecular chaperone proteins and proteasome co mponents. To investigate other protein components of polyglutamine aggregat es, cerebral cortex and striata from patients with Huntington's disease and full-length cDNA transgenic mouse models for this disease were examined im munohistochemically for alpha-synuclein reactivity. Our findings demonstrat e that alpha-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 recr uitment of alpha-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 alpha-synuc lein, may influence disease progression. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.