TY - JOUR
T1 - HD and SCA1
T2 - Tales from two 30-year journeys since gene discovery
AU - Thompson, Leslie M.
AU - Orr, Harry T.
N1 - Publisher Copyright:
© 2023 Elsevier Inc.
PY - 2023/11/15
Y1 - 2023/11/15
N2 - One of the more transformative findings in human genetics was the discovery that the expansion of unstable nucleotide repeats underlies a group of inherited neurological diseases. A subset of these unstable repeat neurodegenerative diseases is due to the expansion of a CAG trinucleotide repeat encoding a stretch of glutamines, i.e., the polyglutamine (polyQ) repeat neurodegenerative diseases. Among the CAG/polyQ repeat diseases are Huntington's disease (HD) and spinocerebellar ataxia type 1 (SCA1), in which the expansions are within widely expressed proteins. Although both HD and SCA1 are autosomal dominantly inherited, and both typically cause mid- to late-life-onset movement disorders with cognitive decline, they each are characterized by distinct clinical characteristics and predominant sites of neuropathology. Importantly, the respective affected proteins, Huntingtin (HTT, HD) and Ataxin 1 (ATXN1, SCA1), have unique functions and biological properties. Here, we review HD and SCA1 with a focus on how their disease-specific and shared features may provide informative insights.
AB - One of the more transformative findings in human genetics was the discovery that the expansion of unstable nucleotide repeats underlies a group of inherited neurological diseases. A subset of these unstable repeat neurodegenerative diseases is due to the expansion of a CAG trinucleotide repeat encoding a stretch of glutamines, i.e., the polyglutamine (polyQ) repeat neurodegenerative diseases. Among the CAG/polyQ repeat diseases are Huntington's disease (HD) and spinocerebellar ataxia type 1 (SCA1), in which the expansions are within widely expressed proteins. Although both HD and SCA1 are autosomal dominantly inherited, and both typically cause mid- to late-life-onset movement disorders with cognitive decline, they each are characterized by distinct clinical characteristics and predominant sites of neuropathology. Importantly, the respective affected proteins, Huntingtin (HTT, HD) and Ataxin 1 (ATXN1, SCA1), have unique functions and biological properties. Here, we review HD and SCA1 with a focus on how their disease-specific and shared features may provide informative insights.
KW - Huntington's disease
KW - polyglutamine neurodegenerative disease
KW - spinocerebellar ataxia type 1
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U2 - 10.1016/j.neuron.2023.09.036
DO - 10.1016/j.neuron.2023.09.036
M3 - Review article
C2 - 37863037
AN - SCOPUS:85176234991
SN - 0896-6273
VL - 111
SP - 3517
EP - 3530
JO - Neuron
JF - Neuron
IS - 22
ER -