Modulating Aging-controlling Pathways in Pre-clinical models of Parkinsonís Disease
Target Validation, 2015
Objective/Rationale: † † † † † ††
Because of its unknown etiology and its link to aging, Parkinsonís disease is often seen as a stochastic and pathological acceleration of aging. Using a high-content screening we recently identified an evolutionary conserved pathway that is a key regulator of aging. Further investigation revealed that this pathway is able to protect nigral dopamine neurons in various cellular and in vivo models of Parkinson.
We will combine different genetic approaches to modulate this aging-governing pathway and determine whether this can not only prevent neurodegeneration but also reverse motor and non-motor symptoms in complementary models of Parkinsonís disease. We will also test whether partial inhibition of this signaling pathway is sufficient to provide a therapeutic effect. The impact of these manipulations will be examined using behavioral, histological, molecular and biochemical analysis.
Relevance to Diagnosis/Treatment of Parkinsonís Disease: † † † † † † † † † ††
We propose that the manipulation of pathways governing cellular aging may lead to the identification of interesting therapeutic targets. These pathways can also provide readily detectable biomarkers and a causative links between Parkinsonís disease and its primary risk factor. This project will also help bridge the gap between healthy and pathological aging.
Anticipated Outcome: † † † † †
The possibility of linking a signaling pathway or biological substrates that can be manipulated pharmacologically to the sporadic form of Parkinsonís disease opens exciting avenues of research for therapeutic approaches. If successful, this project will provide a proof-of-concept that the development of specific inhibitors of this pathway may hold great promise for the treatment of Parkinsonís disease.
Assistant Investigator at Telethon Institute of Genetics and Medicine (TIGEM) Ė Telethon Foundation
Location: Pozzuoli, Italy