Grant: Project Grant

Progressive supranuclear palsy (PSP) is a neurodegenerative disease linked to the dysfunction of tau protein. Tau is attached to microtubules, the railways where the transport of proteins takes place in neurons. The most popular hypothesis is that tau detaches from microtubules leading to microtubule disassembly and dysfunction in PSP. However, growing evidence indicates that it could be the opposite, meaning that alterations of microtubules induce tau detachment. PSP is an age-related disease. Our working hypothesis is that during aging, microtubules undergo alterations that predispose to tau detachment upon stressors such inflammation. To test this, we have collected skin biopsies from healthy adults and PSP patients to isolate fibroblasts that can be used to produce neurons. Interestingly, these neurons retain the signature of aging making them the ideal cellular model to study events linked to aging that are involved in the alterations of microtubules. Our preliminary data indicate that microtubules can be altered before tau pathology develops. This will be further explored in the present proposal. We will also determine which genes and pathways induce the alterations of microtubules. These genes and pathways could become therapeutic targets for PSP.