Lipid dysregulation in polyglutamine diseases

Polyglutamine (polyQ) diseases are fatal neurodegenerative disorders caused by pathological CAG repeat expansions in disease-associated genes. They are characterized by progressive motor dysfunction and typically late onset. Although multiple mechanisms have been proposed, accumulating evidence indicates that lipid dysregulation contributes to neuronal dysfunction and degeneration. Lipids are essential for brain development and homeostasis, and disrupted lipid metabolism is implicated across neurodegenerative conditions. Within the polyQ spectrum, Huntington's disease is the best studied and shows strong links between altered lipid pathways and neuronal pathology, whereas the role of lipid dysregulation in other polyQ disorders remains less well defined. In this review, we summarize key lipid functions in the central nervous system, synthesize reported lipid alterations across polyQ diseases, and evaluate the therapeutic potential of targeting lipid metabolism.