Targeting neurotoxic alpha-synuclein aggregates for Parkinson's disease therapy.

SUMMARYParkinsonandapos s diseasePDis the second most prevalent neurodegenerative disorder after Alzheimerandapos s diseaseADaffecting more thanmillion people in the United StatesBecause age is the major risk factorthe prevalence of both diseases is steadily increasing as our population agesPD belongs to the group of protein misfolding neurodegenerative diseases that are due to the misfolding and aggregation of a host proteinWhile many of the steps leading to neurodegeneration in PD are still unknownsynucleinsynappears to be central to the pathological processLewy Bodiesthe neuropathological hallmark of PDare constituted mainly of phosphorylatedaggregatedsynThere is currently no disease modifying treatment for PD or othersynucleinopathies and there is an urgent need for new treatment optionsThe goal of the present phase I STTR application is to develop and validate a high throughput screeningHTSready assay for the large scale unbiased identification of compounds reducing the levels of a recently identifiedhighly neurotoxicform ofsyncalled psynCompletion of the proposed work plan will enable an HTS campaign and open up the way to develop new neuroprotective compoundsthereby addressing a critical barrier to progress in the field of therapeutic intervention for PD and other synucleinopathies!!Parkinsonandapos s disease is a neurodegenerative disease affecting over a million people in the United Statesfor which there are only symptomatic treatmentsA host proteincalledsynucleinforms neurotoxic aggregates in the brains of affected patientsThis phase I project will enable the discovery of chemical compounds reducing the amounts of toxicsynucleinopening up the way to develop disease modifying drugs