Divalent cations influence htt aggregation but only in the presence of lipid membranes

Abstract

Huntington’s Disease (HD) is caused by an abnormal expansion of the polyglutamine (polyQ) domain within the first exon of the huntingtin protein (htt). This expansion promotes the accumulation of amyloid aggregates associated with HD. Amyloid formation is a complex heterogenous process involving an array of aggregate species such as oligomers, protofibrils, and fibrils. Htt associates with a variety of membranes within cells, including the endoplasmic reticulum (ER). The accumulation of htt fibrils near the ER is associated with membrane abnormalities, resulting in ER damage and calcium leakage.