Stem Cell Institute Philippines

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Stem Cell Treatment for Huntington's Disease is an Option at ASCI

Stem Cell Treatment for Huntington's Disease

 

 

 

 

 

 

 

 

 

 

Stem Cell Treatment for Huntington's Disease is an Option at ASCI

 

Phosphorylation of huntingtin at residue T3 is decreased in Huntington's disease and modulates mutant huntingtin protein conformation. Proc Natl Acad Sci U S A. 2017 Nov 21;: Authors: Cariulo C, Azzollini L, Verani M, Martufi P, Boggio R, Chiki A, Deguire SM, Cherubini M, Gines S, Marsh JL, Conforti P, Cattaneo E, Santimone I, Squitieri F, Lashuel HA, Petricca L, Caricasole A Abstract Posttranslational modifications can have profound effects on the biological and biophysical properties of proteins associated with misfolding and aggregation. However, their detection and quantification in clinical samples and an understanding of the mechanisms underlying the pathological properties of misfolding- and aggregation-prone proteins remain a challenge for diagnostics and therapeutics development. We have applied an ultrasensitive immunoassay platform to develop and validate a quantitative assay for detecting a posttranslational modification (phosphorylation at residue T3) of a protein associated with polyglutamine repeat expansion, namely Huntingtin, and characterized its presence in a variety of preclinical and clinical samples. We find that T3 phosphorylation is greatly reduced in samples from Huntington's disease models and in Huntington's disease patients, and we provide evidence that bona-fide T3 phosphorylation alters Huntingtin exon 1 protein conformation and aggregation properties. These findings have significant implications for both mechanisms of disease pathogenesis and the development of therapeutics and diagnostics for Huntington's disease. PMID: 29162692 [PubMed - as supplied by publisher]
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