Entry Name Huntington disease
Description Huntington disease (HD) is an autosomal-dominant neurodegenerative disorder that primarily affects medium spiny striatal neurons (MSN). The symptoms are choreiform, involuntary movements, personality changes and dementia. HD is caused by a CAG repeat expansion in the IT15 gene, which results in a long stretch of polyglutamine (polyQ) close to the amino-terminus of the HD protein huntingtin (Htt). Mutant Htt (mHtt) has effects both in the cytoplasm and in the nucleus. Full-length huntingtin is cleaved by proteases in the cytoplasm, leading to the formation of cytoplasmic and neuritic aggregates. mHtt also alters vesicular transport and recycling, causes cytosolic and mitochondrial Ca2+ overload, triggers endoplasmic reticulum stress through proteasomal dysfunction, and impairs autophagy function, increasing neuronal death susceptibility. N-terminal fragments containing the polyQ strech translocate to the nucleus where they impair transcription and induce neuronal death.
Class Human Diseases; Neurodegenerative diseaseBRITE hierarchy
Pathway map Disease Reference Authors Landles C, Bates GP
Title Huntingtin and the molecular pathogenesis of Huntington's disease. Fourth in molecular medicine review series.
Journal Reference Authors Borrell-Pages M, Zala D, Humbert S, Saudou F
Title Huntington's disease: from huntingtin function and dysfunction to therapeutic strategies.
Journal Reference Authors Bossy-Wetzel E, Petrilli A, Knott AB
Title Mutant huntingtin and mitochondrial dysfunction.
Journal Reference Authors Cattaneo E, Zuccato C, Tartari M
Title Normal huntingtin function: an alternative approach to Huntington's disease.
Journal Reference Authors Bezprozvanny I, Hayden MR
Title Deranged neuronal calcium signaling and Huntington disease.
Journal Reference Authors Sawa A, Tomoda T, Bae BI
Title Mechanisms of neuronal cell death in Huntington's disease.
Journal Reference Authors Ross CA.
Title Polyglutamine pathogenesis: emergence of unifying mechanisms for Huntington's disease and related disorders.
Journal Reference Authors Ross CA
Title Huntington's disease: new paths to pathogenesis.
Journal Reference Authors Coffey ET
Title Nuclear and cytosolic JNK signalling in neurons.
Journal Reference Authors Morfini GA, You YM, Pollema SL, Kaminska A, Liu K, Yoshioka K, Bjorkblom B, Coffey ET, Bagnato C, Han D, Huang CF, Banker G, Pigino G, Brady ST
Title Pathogenic huntingtin inhibits fast axonal transport by activating JNK3 and phosphorylating kinesin.
Journal Reference Authors Kumar P, Kumar D, Jha SK, Jha NK, Ambasta RK
Title Ion Channels in Neurological Disorders.
Journal Reference Authors Proft J, Weiss N
Title Rectifying rectifier channels in Huntington disease.
Journal Reference Authors Tang TS, Slow E, Lupu V, Stavrovskaya IG, Sugimori M, Llinas R, Kristal BS, Hayden MR, Bezprozvanny I
Title Disturbed Ca2+ signaling and apoptosis of medium spiny neurons in Huntington's disease.
Journal Reference Authors Mackay JP, Nassrallah WB, Raymond LA
Title Cause or compensation?-Altered neuronal Ca(2+) handling in Huntington's disease.
Journal Reference Authors Mattson MP.
Title Accomplices to neuronal death.
Journal Reference Authors McGill JK, Beal MF
Title PGC-1alpha, a new therapeutic target in Huntington's disease?
Journal Reference Authors Intihar TA, Martinez EA, Gomez-Pastor R
Title Mitochondrial Dysfunction in Huntington's Disease; Interplay Between HSF1, p53 and PGC-1alpha Transcription Factors.
Journal Reference Authors La Spada AR, Morrison RS
Title The power of the dark side: Huntington's disease protein and p53 form a deadly alliance.
Journal Reference Authors Lesort M, Chun W, Tucholski J, Johnson GV
Title Does tissue transglutaminase play a role in Huntington's disease?
Journal Reference Authors Bae BI, Xu H, Igarashi S, Fujimuro M, Agrawal N, Taya Y, Hayward SD, Moran TH, Montell C, Ross CA, Snyder SH, Sawa A
Title p53 mediates cellular dysfunction and behavioral abnormalities in Huntington's disease.
Journal Reference Authors Li SH, Cheng AL, Zhou H, Lam S, Rao M, Li H, Li XJ
Title Interaction of Huntington disease protein with transcriptional activator Sp1.
Journal Reference Authors Vidal RL, Matus S, Bargsted L, Hetz C
Title Targeting autophagy in neurodegenerative diseases.
Journal Reference Authors Shibata M, Lu T, Furuya T, Degterev A, Mizushima N, Yoshimori T, MacDonald M, Yankner B, Yuan J
Title Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1.
Journal Related map04141 Protein processing in endoplasmic reticulum
KO pathway
