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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: zQ175\u0394neo. We entirely describe the dynamics of behavioral, neuropathological, and immunohistological changes from 15\u201357 weeks of age. Specifically, zQ175\u0394neo 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.<\/jats:p>","DOI":"10.3390\/ijms232314763","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T01:58:46Z","timestamp":1669600726000},"page":"14763","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["A Novel Huntington\u2019s Disease Assessment Platform to Support Future Drug Discovery and Development"],"prefix":"10.3390","volume":"23","author":[{"given":"Jingyun","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Pathology, Section of Neuropathology, Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo and Oslo University Hospital, Sognsvannsveien 20, 0372 Oslo, Norway; <uri>www.pahnkelab.eu<\/uri>"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4535-9952","authenticated-orcid":false,"given":"Luisa","family":"M\u00f6hle","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section of Neuropathology, Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo and Oslo University Hospital, Sognsvannsveien 20, 0372 Oslo, Norway; <uri>www.pahnkelab.eu<\/uri>"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7060-6564","authenticated-orcid":false,"given":"Thomas","family":"Br\u00fcning","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section of Neuropathology, Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo and Oslo University Hospital, Sognsvannsveien 20, 0372 Oslo, Norway; <uri>www.pahnkelab.eu<\/uri>"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iv\u00e1n","family":"Eiriz","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section of Neuropathology, Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo and Oslo University Hospital, Sognsvannsveien 20, 0372 Oslo, Norway; <uri>www.pahnkelab.eu<\/uri>"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4314-4800","authenticated-orcid":false,"given":"Muhammad","family":"Rafehi","sequence":"additional","affiliation":[{"name":"Institute of Clinical Pharmacology, University Medical Center G\u00f6ttingen, Robert-Koch-Str. 40, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Stefan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section of Neuropathology, Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo and Oslo University Hospital, Sognsvannsveien 20, 0372 Oslo, Norway; <uri>www.pahnkelab.eu<\/uri>"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2048-8598","authenticated-orcid":false,"given":"Sven Marcel","family":"Stefan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section of Neuropathology, Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo and Oslo University Hospital, Sognsvannsveien 20, 0372 Oslo, Norway; <uri>www.pahnkelab.eu<\/uri>"},{"name":"Pahnke Lab (Drug Development and Chemical Biology), L\u00fcbeck Institute of Experimental Dermatology (LIED), University of L\u00fcbeck and University Medical Center Schleswig-Holstein, Ratzeburger Allee 160, 23538 L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7355-4213","authenticated-orcid":false,"given":"Jens","family":"Pahnke","sequence":"additional","affiliation":[{"name":"Department of Pathology, Section of Neuropathology, Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo and Oslo University Hospital, Sognsvannsveien 20, 0372 Oslo, Norway; <uri>www.pahnkelab.eu<\/uri>"},{"name":"Pahnke Lab (Drug Development and Chemical Biology), L\u00fcbeck Institute of Experimental Dermatology (LIED), University of L\u00fcbeck and University Medical Center Schleswig-Holstein, Ratzeburger Allee 160, 23538 L\u00fcbeck, Germany"},{"name":"Department of Pharmacology, Faculty of Medicine, University of Latvia, Jelgavas iela 4, 1004 R\u012bga, Latvia"},{"name":"Department of Neurobiology, The Georg S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15005","DOI":"10.1038\/nrdp.2015.5","article-title":"Huntington disease","volume":"1","author":"Bates","year":"2015","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/S1474-4422(10)70245-3","article-title":"Huntington\u2019s disease: From molecular pathogenesis to clinical treatment","volume":"10","author":"Ross","year":"2011","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1136\/jnnp.56.1.98","article-title":"Duration of illness in Huntington\u2019s disease is not related to age at onset","volume":"56","author":"Roos","year":"1993","journal-title":"J. Neurol. Neurosurg. 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