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Nanoscopic Insights of Amphiphilic Peptide against the Oligomer Assembly Process to Treat Huntington's Disease
Author(s) -
He RueiYu,
Lai XiangMe,
Sun ChiaSui,
Kung TeShien,
Hong JhuYing,
Jheng YuSong,
Liao WeiNeng,
Chen JenKun,
Liao YungFeng,
Tu PangHsien,
Huang Joseph JenTse
Publication year - 2020
Publication title -
advanced science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.388
H-Index - 100
ISSN - 2198-3844
DOI - 10.1002/advs.201901165
Subject(s) - huntingtin , oligomer , huntingtin protein , huntington's disease , amphiphile , peptide , in vivo , chemistry , biophysics , nanotechnology , mutant , microbiology and biotechnology , computational biology , biology , biochemistry , disease , materials science , medicine , organic chemistry , pathology , copolymer , gene , polymer
Finding an effective therapeutic regimen is an urgent demand for various neurodegenerative disorders including Huntington's disease (HD). For the difficulties in observing the dynamic aggregation and oligomerization process of mutant Huntingtin (mHtt) in vivo, the evaluation of potential drugs at the molecular protein level is usually restricted. By combing lifetime‐based fluorescence microscopies and biophysical tools, it is showcased that a designed amphiphilic peptide, which targets the mHtt at an early stage, can perturb the oligomer assembly process nanoscopically, suppress the amyloid property of mHtt, conformationally transform the oligomers and/or aggregates of mHtt, and ameliorate mHtt‐induced neurological damage and aggregation in cell and HD mouse models. It is also found that this amphiphilic peptide is able to transport to the brain and rescue the memory deficit through intranasal administration, indicating its targeting specificity in vivo. In summary, a biophotonic platform is provided to investigate the oligomerization/aggregation process in detail that offers insight into the design and effect of a targeted therapeutic agent for Huntington's disease.

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