Huntington’s 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—most 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.
Araldi et al. (Thu,) studied this question.