TY - JOUR
T1 - Huntington's disease
AU - Ross, Christopher A.
AU - Margolis, Russell L.
N1 - Funding Information:
Supported by NIH NS 16375, 34172, 38144 and 38054, and grants from the HDSA and HDF. The authors thank the staff of the Baltimore HD Center, founded by Dr Paul McHugh, Dr Susan Folstein and Dr Marshal Folstein. We thank Dr McHugh and the Department of Psychiatry for support. Finally, the authors wish to thank their patients with HD and their families for their inspiration, patience and cooperation. Parts of this review were adapted from previously published material [8,101,102] with permission from the publishers.
PY - 2001
Y1 - 2001
N2 - Huntington's disease (HD) is an autosomal dominant progressive neuropsychiatric disorder, characterized by abnormalities of movement, emotion and cognition. The most important pathological feature is selective neuronal loss, primarily in the striatum and cerebral cortex. HD is caused by the expansion of a CAG trinucleotide repeat in the gene encoding huntingtin. The expanded repeat encodes an abnormally long polyglutamine tract, and many lines of evidence now strongly suggest that this mutation is neurotoxic. In this review, we first detail the clinical, genetic and pathological features of HD. We then describe how clues from neurotoxicological, biochemical, cell, transgenic mouse, and invertebrate models of HD lead to a multifactored model of HD pathogenesis. We conclude by discussing how the model of HD serves as a guide to the development of rational therapeutics for this devastating disease.
AB - Huntington's disease (HD) is an autosomal dominant progressive neuropsychiatric disorder, characterized by abnormalities of movement, emotion and cognition. The most important pathological feature is selective neuronal loss, primarily in the striatum and cerebral cortex. HD is caused by the expansion of a CAG trinucleotide repeat in the gene encoding huntingtin. The expanded repeat encodes an abnormally long polyglutamine tract, and many lines of evidence now strongly suggest that this mutation is neurotoxic. In this review, we first detail the clinical, genetic and pathological features of HD. We then describe how clues from neurotoxicological, biochemical, cell, transgenic mouse, and invertebrate models of HD lead to a multifactored model of HD pathogenesis. We conclude by discussing how the model of HD serves as a guide to the development of rational therapeutics for this devastating disease.
KW - Glutamine
KW - Huntington
KW - Movement
KW - Neurodegeneration
KW - Psychiatric
KW - Trinucleotide repeat
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U2 - 10.1016/S1566-2772(00)00014-1
DO - 10.1016/S1566-2772(00)00014-1
M3 - Article
AN - SCOPUS:0001337742
SN - 1566-2772
VL - 1
SP - 142
EP - 152
JO - Clinical Neuroscience Research
JF - Clinical Neuroscience Research
IS - 1-2
ER -