{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T20:34:52Z","timestamp":1780691692085,"version":"3.54.1"},"reference-count":270,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo (FAPESP)","award":["2023\/06116-2"],"award-info":[{"award-number":["2023\/06116-2"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo (FAPESP)","award":["2023\/10353-0"],"award-info":[{"award-number":["2023\/10353-0"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo (FAPESP)","award":["2024\/07829-5"],"award-info":[{"award-number":["2024\/07829-5"]}]},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo (FAPESP)","award":["2024\/17577-3"],"award-info":[{"award-number":["2024\/17577-3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Huntington\u2019s disease (HD) is an autosomal dominant neurodegenerative disorder characterized by progressive motor dysfunction, psychiatric disturbances, and cognitive decline. The pathophysiology of HD centers on a polyglutamine expansion in the huntingtin protein, which triggers widespread transcriptional dysregulation, impaired proteostasis, mitochondrial dysfunction, and excitotoxic neuronal loss\u2014most prominently within the striatum and cortex. Despite decades of research, disease-modifying therapies remain elusive. This review synthesizes how the emerging integration of translational bioinformatics, spotlighting artificial intelligence-driven transcriptomic analyses, has identified transcriptional signatures correlating with disease progression and therapeutic response. These integrative approaches hold promise for accelerating the bench-to-bedside translation of HD therapeutics, positioning AI-powered discovery as a frontier for overcoming the complexity of neurodegeneration.<\/jats:p>","DOI":"10.3390\/brainsci15080865","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T15:44:21Z","timestamp":1755186261000},"page":"865","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["AI-Enhanced Transcriptomic Discovery of Druggable Targets and Repurposed Therapies for Huntington\u2019s Disease"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8288-2577","authenticated-orcid":false,"given":"Rodrigo Pinheiro","family":"Araldi","sequence":"first","affiliation":[{"name":"BioDecision Analytics Ltd., S\u00e3o Paulo 04021-001, Brazil"},{"name":"Structural and Functional Post-Graduation Program, Paulista School of Medicine, Federal University of S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo 04021-001, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Rafael","family":"Dias Pinto","sequence":"additional","affiliation":[{"name":"BioDecision Analytics Ltd., S\u00e3o Paulo 04021-001, Brazil"},{"name":"Structural and Functional Post-Graduation Program, Paulista School of Medicine, Federal University of S\u00e3o Paulo (UNIFESP), S\u00e3o Paulo 04021-001, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Kerkis","sequence":"additional","affiliation":[{"name":"Genetics Laboratory, Butantan Institute, S\u00e3o Paulo 05503-900, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1002\/mds.29228","article-title":"Prevalence and Incidence of Huntington\u2019s Disease: An Updated Systematic Review and Meta-Analysis","volume":"37","author":"Medina","year":"2022","journal-title":"Mov. 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