Role of the Coiled-coil structure of the Huntingtin protein in the intercellular propagation of polyQ aggregates and in the progression of the disease

The pathogenesis of the neurodegenerative and inherited disorder Huntington Disease (HD) is intimately linked to the formation of Hungtintin (Htt) protein aggregates that from a confined region of the brain in the early stages of the disease spread to distant areas in the nervous system. How the aggregates of Htt protein spread among neurons is currently unknown. However, recent works on the pathology of Alzheimer's and Parkinson's disorders show that prion-like intercellular transmission of protein aggregates may contribute to the spread of neurodegenerative diseases. I have found that Htt is released from cells by exocytosis and that it can be uptaken by other cells. Moreover, an aggregation prone and pathological Htt mutant shows enhanced intercellular spreading capabilities. These findings could explain the molecular basis of the progression of the disorder, providing new therapeutic targets and avenues of research in the battle against this yet incurable disorder