Huntingtin-Associated Protein Related Biomarkers in Neural Survival

The prevalence of neurodegenerative disorders is increasing due to the aging population. New intervention and monitoring biomarkers are required. Huntington Disease (HD) is a well-established model for the research of neurodegeneration due to its single causative gene mutation. The HD protein, huntingtin (Htt), and the first identified partner, huntingtin-associated protein-1 (Hap1), were found to associate with microtubule-dependent motor proteins, and involved in the transport of various protein complexes and membrane receptors. These two proteins are both essential for animal survival. Evidence showed that mutations of proteins involved in microtubule-dependent trafficking often induce neuronal pathologies including neurodegeneration. Our recent study showed a decrease of neuron population in Hap1-defecient mice. Indeed, a proteomic analysis revealed that there were many proteins, known as regulators of cell proliferation and survival, reduced association with microtubules in Hap1-defecient mouse brain. In this proposal, we will specify the molecular roles of some Hap1-related biomarkers in neural development, survival and degeneration.