Polyglutamine repeats

In Huntington s disease the polyglutamine repeat expansion in exon 1 of HD leads to a toxic gain of the protein huntingtin (htt). Harper et al. could show that siRNA directed against mutant human htt reduced htt iriRNA and protein expression in cell culture and in HD... 

Davies SW, Beardsall K, Turmaine M, DiFiglia M, Aronin N, Bates GP. Are neuronal intranuclear inclusions the common neuropathology of triplet-repeat disorders with polyglutamine-repeat expansions Lancet 1998 351 131-133. 

Bates GP, Mangiarini L, Davies SW. Transgenic mice in the study of polyglutamine repeat expansion diseases. Brain Pathol 1998 8 699-714. 

Polyglutamine repeat 146 unit CAG repeat inserted in hprt gene -... 

Merlino, A., Esposito, L., and Vitagliano, L. (2006). Polyglutamine repeats and beta-helix structure Molecular dynamics study. Proteins 63(4), 918-927. 

SBMA In addition to HD, NaBu has also been reported to be effective in treating spinal and bulbar muscular atrophy (SBMA) (Minamiyama et al, 2004), an inheritable motorneuron disease caused by an expanded polyglutamine-repeat within the androgen receptor. SBMA is associated with motorneuron loss in the spinal cord and brain stem as well as a sub-clinical loss of sensory neurons in the dorsal root ganglia resulting in skeletal muscle atrophy and weakness (Sobue et al, 1989 ... 

Salminen A, Tapiola T, Korhonen P, Suuronen T (1998) Neuronal optosis induced by histone deacetylase inhibitors. Brain Res Mol Brain Res 61(l-2) 203-206 Sanchez I, Xu CJ, Juo P, Kakizaka A, Blenis J, Yuan J (1999) Caspase-8 is required for cell death induced by expanded polyglutamine repeats. Neuron 22(3) 623-633 Sanchez I, Mahlke C, Yuan J (2003) Pivotal role of oligomerization in expanded polyglutamine neurode-generative disorders. Nature 421(6921) 373-379... 

Sanchez I, Xu CJ, Juo P, Kakizaka A, Blenis J, Yuan J (1999) Caspase-8 is required for cell death induced by expanded polyglutamine repeats. Neuron 22 623-633... 

Matsuyama Z, Yanagisawa NK, Aoki Y, Black JL 3rd, Lennon VA, Mori Y, Imoto K, Inuzuka T (2004) Polyglutamine repeats of spinocerebeUar ataxia 6 impair the cell-death-preventing effect of CaV2.1 Ca channel - loss of-fimction cellular model of SCA6. Neurobiol Dis 17 198-204... 

Huntington s disease Human huntingtin with expanded polyglutamine repeats Local... 

Proteins with an expanded polyglutamine repeat are more resistant to proteasomal degradation [53]. Inhibition of the proteasome also induced accumulation of aggregated forms of a viral nucleoprotein reported by Anton et al. [54]. Recently was found an inhibition of the proteasome in a transfected cell line with a protein FLAG-F508 and with the Huntingtin protein [55]. 

Ikehara Y, Shimizu N, Kono M, Nishihara S, Nakanishi H, Kitamura T, Narimatsu H, Tsuji S, Tatematsu M (1999) A novel glycosyltransferase wifii a polyglutamine repeat a new candidate for GDla synthase (ST6GalNAc V)(l). FEBS Lett 463 92-96... 

Bao J, Sharp AH, Wagster MV, Becher M, Schilling G> Ross CA, et al. Expansion of polyglutamine repeat in huntingtin leads to abnormal protein interactions involving calmodulin. Proc Natl Acad Sci USA 1996 93 5037-42. 

Riley BE, Zoghbi HY, Orr HT (2005) SUMOylation of the polyglutamine repeat protein, ataxin-1, is dependent on a functional nuclear localization signal. J Biol Chem 280(23) 21942-21948... 

Alterations in UPS fnnction have been implicated in the pathogenesis of a variety of sporadic and familial neurodegenerative diseases including Parkinson disease, Alzheimer disease, polyglutamine repeat diseases, and ALS [63-65]. Mizuno et al. [66] called VCP "vacuole-creating protein" and demonstrated that VCP was observed in ubiquitin-positive intraneuronal inclusions in both motor neuron disease with dementia, and ballooned neurons in Creutzfeldt-Jakob disease. In Alzheimer disease, VCP has been found in dystrophic neurites while... 

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