Multiple pathways contribute to the pathogenesis of Huntington disease

HD Lighthouse Contributing Editor's Comment: This extensive review of what is known about HD pathology is very helpful for reminding us what we have learned and what we still don't know.

-- Marsha L. Miller, Ph.D.
Posted to the HDL: 12-25-2006

Shi-Hua Li, Ph.D., Assistant Professor of Human Genetics, Emory University School of Medicine

Shi-Hua Li and Xiao-Jiang Li

ABSTRACT: Huntington disease (HD) is caused by expansion of a polyglutamine (polyQ) domain in the protein known as huntingtin (htt), and the disease is characterized by selective neurodegeneration. Expansion of the polyQ domain is not exclusive to HD, but occurs in eight other inherited neurodegenerative disorders that show distinct neuropathology. Yet in spite of the clear genetic defects and associated neurodegeneration seen with all the polyQ diseases, their pathogenesis remains elusive. The present review focuses on HD, outlining the effects of mutant htt in the nucleus and neuronal processes as well as the role of cell-cell interactions in HD pathology. The widespread expression and localization of mutant htt and its interactions with a variety of proteins suggest that mutant htt engages multiple pathogenic pathways. Understanding these pathways will help us to elucidate the pathogenesis of HD and to target therapies effectively.

Source: Molecular Neurodegeneration 2006 Dec 16;1(1):19 [Epub ahead of print]