Premium
Metabolism in HD: Still a relevant mechanism?
Author(s) -
Duan Wenzhen,
Jiang Mali,
Jin Jing
Publication year - 2014
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.25992
Subject(s) - huntingtin , neurodegeneration , pathogenesis , huntington's disease , biology , bioenergetics , mitochondrion , huntingtin protein , mechanism (biology) , trinucleotide repeat expansion , neuroscience , mutant , microbiology and biotechnology , genetics , disease , medicine , gene , immunology , allele , philosophy , epistemology
The polyglutamine expansion within huntingtin is the causative factor in the pathogenesis of Huntington's disease (HD). Although the underlying mechanisms by which mutant huntingtin causes neuronal dysfunction and degeneration have not been fully elucidated, compelling evidence suggests that mitochondrial dysfunction and compromised energy metabolism are key players in HD pathogenesis. Longitudinal studies of HD subjects have shown reductions in glucose utilization before the disease clinical onset. Preferential striatal neurodegeneration, a hallmark of HD pathogenesis, also has been associated with interrupted energy metabolism. Data from genetic HD models indicate that mutant huntingtin disrupts mitochondrial bioenergetics and prevents adenosine triphosphate (ATP) generation, implying altered energy metabolism as an important component of HD pathogenesis. Here we revisit the evidence of abnormal energy metabolism in the central nervous system of HD patients, review our current understanding of the molecular mechanisms underlying abnormal metabolism induced by mutant huntingtin, and discuss the promising therapeutic development by halting abnormal metabolism in HD. © 2014 International Parkinson and Movement Disorder Society