Protein aggregates in Huntington's disease.

Abstract

Huntington's disease (HD) is an incurable neurodegenerative disease characterized by abnormal motor movements, personality changes, and early death. HD is caused by a mutation in the IT-15 gene that expands abnormally the number of CAG nucleotide repeats. As a result, the translated protein huntingtin contains disease-causing expansions of glutamines (polyQ) that make it prone to misfold and aggregate. While the gene and mutations that cause HD are known, the mechanisms underlying HD pathogenesis are not. Here we will review the state of knowledge of HD, focusing especially on a hallmark pathological feature-intracellular aggregates of mutant Htt called inclusion bodies (IBs). We will describe the role of IBs in the disease. We speculate that IB formation could be just one component of a broader coping response triggered by misfolded Htt whose efficacy may depend on the extent to which it clears toxic forms of mutant Htt. We will describe how IB formation might be regulated and which factors could determine different coping responses in different subsets of neurons. A differential regulation of IB formation as a function of the cellular context could, eventually, explain part of the neuronal vulnerability observed in HD.

• Authors: Montserrat Arrasate, Steven Finkbeiner
• Journal: Experimental neurology (Exp Neurol) Vol. 238 Issue 1 Pg. 1-11 (Nov 2012) ISSN: 1090-2430 [Electronic] United States
• PMID: 22200539 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• HTT protein, human
• Huntingtin Protein
• Nerve Tissue Proteins

Topics

• Animals
• Humans
• Huntingtin Protein
• Huntington Disease (genetics, metabolism, pathology)
• Inclusion Bodies (pathology, physiology)
• Mutation (genetics, physiology)
• Nerve Tissue Proteins (genetics, metabolism)