Uncovering hidden protein networks in Huntington’s disease: implications for pathogenesis and therapy

Ubiquitin-Proteasome Dysfunction in Huntington's Disease and Its Mechanistic Insights and Druggable Targets Across the Proteostasis Network

Huntington's disease (HD) offers a particularly instructive, if sobering, window into what happens when a cell's protein-clearance machinery is asked to do more than it can bear. Background: the ubiquitin-proteasome system (UPS) is the principal route by which short-lived and misfolded proteins are removed from eukaryo...

Targeting Klotho Signaling for Neuroprotection in Huntington's Disease: A Comprehensive Review.

Klotho is a promising neurochemical modulator with disease-modifying properties in HD, and its multifunctional protective activities are consistent with important pathological markers of HD, necessitating more preclinical and clinical studies to confirm its translational value.

Missense mutations in the SNCA gene: Molecular mechanisms and clinical implications.

The molecular architecture of the SNCA gene is outlined, including regulatory regions, alternative splicing, and untranslated regions that influence αSyn expression and isoform diversity, and seven missense mutations of the SNCA gene are discussed in detail from the genomic level, extending to phenotypic presentations.

Genetic architecture and molecular pathogenesis of Parkinson’s disease: emerging mechanisms and therapeutic targets

Defective membrane dynamics in Huntington's disease: A role of Rab11 dysfunction.

Huntington's disease (HD) is a life-threatening neurodegenerative disease caused by a mutation in Huntingtin (HTT). Neuropathology in HD is marked by a progressive loss of neurons in the caudate putamen and the deposition of mutant HTT aggregates as cytoplasmic and nuclear inclusions. At present, no disease-modifying t...

Current landscape and future perspectives of small-molecule therapeutics for Huntington's disease: From rational design to clinical translation.

This review critically summarizes the design, synthesis, and structural motifs of small-molecule candidates, clinically used agents, and antioxidant natural products, providing a structural framework to guide the rational design and development of next-generation anti-HD compounds.