Research Area
Aging

Grant Type
Network

Year
2014

Abstract

The purpose of this grant is to further understand the role of the inflammation present in the aging brain in PD, towards testing anti-inflammatory compounds for their ability to prevent the progression of this chronic neurodegenerative disorder. Parkinson’s disease is a disorder of aging, its incidence skyrockets in the later decades of life. The environment of the aging brain is less able to deal with the stress that is a biproduct of daily cellular function; this stress leads to inflammation, which has been shown to contribute to disease progression. This grant proposes to study aging-induced inflammation in both human cells from PD patients (project 1 – Gage), and mouse models of PD (project 2 – Masliah) to further understand the connection
between inflammation and neurodegeneration. The Gage lab has taken skin samples from 12 patients with PD and eight unaffected control subjects, turned them back into stem cells, and then guided them down the developmental pathway to become neurons. These human disease-specific neurons are an incredibly powerful research tool that can be used to understand the biology of disease processes in a dish. The Gage lab has also already identified anti-inflammatory compounds that are neuro-protective in unaffected human neurons, and this grant proposes testing those compounds in the human PD neurons and Dr. Masliah’s PD animal models. The Glass laboratory will use its gene sequencing abilities to illuminate the pathways that are disrupted in aging and inflammation in PD, and also which pathways are being activated by the anti-inflammatory compounds. The technology pioneered by the Glass lab allows us to take a snapshot of the proteins each cell is making, called its expression profile. We plan to compare the expression profiles of PD cells against their unaffected controls, and also PD cells treated with anti-inflammatory compounds against untreated ones to understand how the cells are affected in both cases. The goal of this project is to illuminate inflammation-based deficits in human and mouse neurons affected with PD, and test anti-inflammatory molecules as a novel therapeutic approach towards delaying the disease progression.