Differential vulnerability of neurons in Huntington's disease: the role of cell type-specific features.
Abnormal expansion of a polyglutamine tract in huntingtin (Htt) protein results in Huntington's disease (HD), an autosomal dominant neurodegenerative disorder involving progressive loss of motor and cognitive function. Contrasting with the ubiquitous tissue expression of polyglutamine-expanded Htt, HD pathology is characterized by the increased vulnerability of specific neuronal populations within the striatum and the cerebral cortex. Morphological, biochemical, and functional characteristics of neurons affected in HD that might render these cells more vulnerable to the toxic effects of polyglutamine-Htt are covered in this review. The differential vulnerability of neurons observed in HD is discussed in the context of various major pathogenic mechanisms proposed to date, and in line with evidence showing a 'dying-back' pattern of degeneration in affected neuronal populations.
Department of Anatomy and Cell Biology. University of Illinois at Chicago, Chicago, Illinois 60612, USA.
Ina
I
Han
YiMei
Y
You
Jeffrey H
JH
Kordower
Scott T
ST
Brady
Gerardo A
GA
Morfini
D001370:Axonal Transport / Q000502:physiology; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000502:physiology; D015870:Gene Expression / Q000235:genetics / Q000502:physiology; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D008928:Mitochondria / Q000473:pathology; D009154:Mutation / Q000502:physiology; D009410:Nerve Degeneration / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000633:toxicity; D009474:Neurons / Q000145:classification / Q000473:pathology*; D009687:Nuclear Proteins / Q000235:genetics / Q000633:toxicity; D015398:Signal Transduction
D019208:Brain-Derived Neurotrophic Factor; C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins