Huntingtin proteolysis releases non‐polyQ fragments that cause toxicity through dynamin 1 dysregulation
نویسندگان
چکیده
منابع مشابه
Huntingtin proteolysis releases non-polyQ fragments that cause toxicity through dynamin 1 dysregulation.
Cleavage of mutant huntingtin (HTT) is an essential process in Huntington's disease (HD), an inherited neurodegenerative disorder. Cleavage generates N-ter fragments that contain the polyQ stretch and whose nuclear toxicity is well established. However, the functional defects induced by cleavage of full-length HTT remain elusive. Moreover, the contribution of non-polyQ C-terminal fragments is u...
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As you can see below, the referees appreciate the characterization of C-terminal HTT fragments that promotes toxicity via modulating ER stress. However, they also raise a number of issues that would have to be resolved in order for consideration here. A major issue to resolve is the need to provide further data in support of that C-terminal HTT-mediated toxicity is relevant for disease. Should ...
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Huntington's disease (HD) is a fatal autosomal dominant neurodegenerative disorder caused by a trinucleotide (CAG)(n) repeat expansion in the coding sequence of the huntingtin gene, and an expanded polyglutamine (>37Q) tract in the protein. This results in misfolding and accumulation of huntingtin protein (htt), formation of neuronal intranuclear and cytoplasmic inclusions, and neuronal dysfunc...
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Amino-terminal fragments of huntingtin, which contain the expanded polyglutamine repeat, have been proposed to contribute to the pathology of Huntington's disease (HD). Data supporting this claim have been generated from patients with HD in which truncated amino-terminal fragments forming intranuclear inclusions have been observed, and from animal and cell-based models of HD where it has been d...
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Proteolytic cleavage of huntingtin (Htt) is known to be a key event in the pathogenesis of Huntington's disease (HD). Our understanding of proteolytic processing of Htt has thus far focused on the protease families-caspases and calpains. Identifying critical proteases involved in Htt proteolysis and toxicity using an unbiased approach has not been reported. To accomplish this, we designed a hig...
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ژورنال
عنوان ژورنال: The EMBO Journal
سال: 2015
ISSN: 0261-4189,1460-2075
DOI: 10.15252/embj.201490808