Nanoscopic Insights of Amphiphilic Peptide against the Oligomer Assembly Process to Treat Huntington’s Disease.

Publication date: Jan 01, 2020

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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He, R.Y., Lai, X.M., Sun, C.S., Kung, T.S., Hong, J.Y., Jheng, Y.S., Liao, W.N., Chen, J.K., Liao, Y.F., Tu, P.H., and Huang, J.J. Nanoscopic Insights of Amphiphilic Peptide against the Oligomer Assembly Process to Treat Huntington’s Disease. 06916. 2020 Adv Sci (Weinh) (7):2.

Concepts Keywords
Amphiphilic Insulin-degrading enzyme
Amyloid Huntingtin
Assembly Amphiphile
Brain Polymer chemistry
Fluorescence Amyloid
Huntingtin Peptide
Huntington Chemical properties
Intranasal Administration Oligomer
Memory Deficit Chemistry
Mutant Physical sciences
Neurodegenerative Disorders Natural sciences
Neurological
Oligomer
Oligomerization
Oligomers
Peptide
Sci
Vivo

Semantics

Type Source Name
disease MESH neurodegenerative disorders
disease MESH memory deficit
drug DRUGBANK Coenzyme M
disease MESH protein misfolding diseases
drug DRUGBANK L-Arginine
disease MESH tryptophan
drug DRUGBANK L-Tryptophan
drug DRUGBANK Water
drug DRUGBANK Tretamine
disease MESH **p
drug DRUGBANK Proline
drug DRUGBANK Tretinoin
drug DRUGBANK Iodine
drug DRUGBANK Esomeprazole
drug DRUGBANK Phosphate ion
disease MESH death
disease MESH immuno
disease MESH Astrocytosis
disease MESH pathological processes
drug DRUGBANK Flunarizine
disease MESH separation
drug DRUGBANK Potassium Chloride
drug DRUGBANK Activated charcoal
drug DRUGBANK Copper
drug DRUGBANK Acetate ion
drug DRUGBANK L-Glutamine
drug DRUGBANK Fluorescein
drug DRUGBANK Pentaerythritol tetranitrate
drug DRUGBANK Hydrogen peroxide
drug DRUGBANK Edetic Acid
drug DRUGBANK L-Tyrosine
drug DRUGBANK Tromethamine
drug DRUGBANK Amino acids
drug DRUGBANK Semagacestat
drug DRUGBANK Ferrous sulfate anhydrous
disease MESH Mody

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