Misfolded protein accumulation and neurodegeneration due to phospholipase gene mutations

2007 Pilot Project Read More

Investigators

Principal Investigator: Paul Kotzbauer, MD, PhD (Wash U Neurology)
Co-investigator: Joy Snider, MD, PhD (WashU Neurology)

Description

Many neurodegenerative disorders are defined by accumulations of misfolded proteins in the brain. Mutations in the gene PLA2G6, which is involved in lipid metabolism, lead to neurodegenerative disorders and accumulation of alpha-synuclein — the same protein that accumulates in the brains of Parkinson’s Disease patients. This project will develop methods to detect misfolded protein accumulation in cultured neurons, and will generate a new animal model of alpha-synuclein overproduction. These new tools will enable the development of therapies to minimize toxicity and improve clearance of misfolded proteins.

Publications

Li M., Husic N., Lin Y., Christensen H., Malik I., McIver S., Daniels C.M., Harris D.A., Kotzbauer P.T., Goldberg M.P., Snider B.J. Optimal promoter usage for lentiviral vector-mediated transduction of cultured central nervous system cells.  Journal of Neuroscience Methods 189(1):56-64, (2010).

Dhavale DD, Tsai C, Bagchi DP, Engel LA, Sarezky J, Kotzbauer PT. A sensitive assay reveals structural requirements for α-synuclein fibril growth. J Biol Chem.;292(22):9034-9050, (2017).

Updated June  2017

Hope Center Investigators

Paul Kotzbauer

Joy Snider