Endothelial Dysfunction in Huntington’s Disease: Pathophysiology and Therapeutic Implications

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(4), С. 1432 - 1432

Опубликована: Фев. 8, 2025

Huntington’s disease (HD) is a progressive neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms. While traditionally viewed through the lens of neuronal dysfunction, emerging evidence highlights critical role endothelial dysfunction in HD pathogenesis. This review provides comprehensive overview HD, drawing on findings from both animal models human studies. Key features include impaired angiogenesis, altered cerebral blood flow, compromised neurovascular coupling cerebrovascular reactivity, increased blood–brain barrier permeability. Genetic factors such as mutant huntingtin protein, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), Brain-derived neurotrophic factor (BDNF), adenosine A2A (ADORA2A) interact to influence function complex ways. Various therapeutic approaches targeting including antioxidants, nitric oxide enhancers, calcium channel blockers, statins, metformin, have shown promise preclinical but face translational challenges, particularly regarding optimal timing intervention patient stratification. The implications these suggest that reconceptualizing disorder, rather than purely neuronal, could lead more effective treatment strategies. Future research priorities should include: (1) developing validated vascular biomarkers for progression, (2) advancing neuroimaging techniques monitor real-time. These directions will be crucial bridging current gap between clinical success vascular-targeted therapeutics.

Язык: Английский

Lactylation as a metabolic epigenetic modification: Mechanistic insights and regulatory pathways from cells to organs and diseases

Metabolism, Год журнала: 2025, Номер unknown, С. 156289 - 156289

Опубликована: Май 1, 2025

Язык: Английский