The regulation of N-terminal Huntingtin (Htt552) accumulation by Beclin1
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چکیده
منابع مشابه
High efficiency adenovirus-mediated expression of truncated N-terminal huntingtin fragment (htt552) in primary rat astrocytes.
Huntington's disease (HD) is caused by an expansion of polyglutamine tract in N-terminus of huntingtin (htt). The mutation of htt leads to dysfunction and premature death of striatal and cortical neurons. However, the effects of htt mutation on glia remain largely unknown. This study aimed to establish a glia HD model using an adenoviral vector to express wild-type and mutant N-terminal hunting...
متن کاملTruncated N-terminal huntingtin fragment with expanded-polyglutamine (htt552-100Q) suppresses brain-derived neurotrophic factor transcription in astrocytes.
Although huntingtin (htt) can be cleaved at many sites by caspases, calpains, and aspartyl proteases, amino acid (aa) 552 was defined as a preferred site for cleavage in human Huntington disease (HD) brains in vivo. To date, the normal function of wild-type N-terminal htt fragment 1-552 aa (htt552) and its pathological roles of mutant htt552 are still unknown. Although mutant htt (mhtt) is also...
متن کاملInhibiting the ubiquitin-proteasome system leads to preferential accumulation of toxic N-terminal mutant huntingtin fragments.
An expanded polyglutamine (polyQ) domain in the N-terminal region of huntingtin (htt) causes misfolding and accumulation of htt in neuronal cells and the subsequent neurodegeneration of Huntington's disease (HD). Clearing the misfolded htt is critical for preventing neuropathology, and this process is mediated primarily by both the ubiquitin-proteasome system (UPS) and autophagy. Although overe...
متن کاملN-terminal Huntingtin Knock-In Mice: Implications of Removing the N-terminal Region of Huntingtin for Therapy
The Huntington's disease (HD) protein, huntingtin (HTT), is a large protein consisting of 3144 amino acids and has conserved N-terminal sequences that are followed by a polyglutamine (polyQ) repeat. Loss of Htt is known to cause embryonic lethality in mice, whereas polyQ expansion leads to adult neuronal degeneration. Whether N-terminal HTT is essential for neuronal development or contributes o...
متن کاملPreferential accumulation of N-terminal mutant huntingtin in the nuclei of striatal neurons is regulated by phosphorylation.
An expanded polyglutamine tract (>37 glutamines) in the N-terminal region of huntingtin (htt) causes htt to accumulate in the nucleus, leading to transcriptional dysregulation in Huntington disease (HD). In HD knock-in mice that express full-length mutant htt at the endogenous level, mutant htt preferentially accumulates in the nuclei of striatal neurons, which are affected most profoundly in H...
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ژورنال
عنوان ژورنال: Acta Pharmacologica Sinica
سال: 2012
ISSN: 1671-4083,1745-7254
DOI: 10.1038/aps.2012.14