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RSS FeedsIJMS, Vol. 23, Pages 14763: A Novel Huntington’s Disease Assessment Platform to Support Future Drug Discovery and Development (International Journal of Molecular Sciences)

 
 

25 november 2022 15:12:56

 
IJMS, Vol. 23, Pages 14763: A Novel Huntington’s Disease Assessment Platform to Support Future Drug Discovery and Development (International Journal of Molecular Sciences)
 


Huntington’s disease (HD) is a lethal neurodegenerative disorder without efficient therapeutic options. The inefficient translation from preclinical and clinical research into clinical use is mainly attributed to the lack of (i) understanding of disease initiation, progression, and involved molecular mechanisms; (ii) knowledge of the possible HD target space and general data awareness; (iii) detailed characterizations of available disease models; (iv) better suitable models; and (v) reliable and sensitive biomarkers. To generate robust HD-like symptoms in a mouse model, the neomycin resistance cassette was excised from zQ175 mice, generating a new line: zQ175Δneo. We entirely describe the dynamics of behavioral, neuropathological, and immunohistological changes from 15–57 weeks of age. Specifically, zQ175Δneo mice showed early astrogliosis from 15 weeks; growth retardation, body weight loss, and anxiety-like behaviors from 29 weeks; motor deficits and reduced muscular strength from 36 weeks; and finally slight microgliosis at 57 weeks of age. Additionally, we collected the entire bioactivity network of small-molecule HD modulators in a multitarget dataset (HD_MDS). Hereby, we uncovered 358 unique compounds addressing over 80 different pharmacological targets and pathways. Our data will support future drug discovery approaches and may serve as useful assessment platform for drug discovery and development against HD.


 
51 viewsCategory: Biochemistry, Biophysics, Molecular Biology
 
IJMS, Vol. 23, Pages 14762: Utility of Human Relevant Preclinical Animal Models in Navigating NAFLD to MAFLD Paradigm (International Journal of Molecular Sciences)
IJMS, Vol. 23, Pages 14761: Down-Regulation of Neogenin Decreases Proliferation and Differentiation of Spermatogonia during the Early Phase of Spermatogenesis (International Journal of Molecular Sciences)
 
 
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