Cofilin-1 as a Major Contributor to Oxidative Stress-mediated Cell Death in Parkinsonís Disease
Rapid Response Innovation Awards, 2014
Oxidative stress, a process that stops the cell producing energy efficiently, is a key cause of the death of neurons in Parkinsonís disease. We have previously shown that oxidative stress also occurs in lung cancer cells, via a process involving a protein called cofilin-1. This protein is also present in the brain, so we want to see whether cofilin-1 is involved in mediating oxidative stress in Parkinsonís, too.
Our study is in two parts. The first will involve using brain tissue taken from patients who have died with Parkinsonís to compare the amount of cofilin-1 protein and the amount of a protein that controls its function (called LIMK) in Parkinsonís and non-Parkinsonís people. This will tell us whether there is any change in the amount of cofilin-1 in Parkinsonís disease. We will also investigate whether changes in the amount of cofilin-1 mirror those of Lewy bodies, clumps of the protein alpha-synuclein present in the brains of patients with Parkinsonís. The second part will take brain cells grown in the laboratory, in which we have genetically altered the amounts and forms of coflin-1 protein they contain, and challenge them with a toxin that causes oxidative stress, to see what effect it has upon the cell. These experiments will tell us whether cofilin-1 promotes oxidative stress.
Relevance to Diagnosis/Treatment of Parkinsonís Disease:
This project will significantly advance our knowledge of a major disease process underway in Parkinsonís, which will provide us with a new target against which we can design drugs that will treat the disease.
We expect that our studies using post-mortem brain tissue will demonstrate that cofilin-1 is altered in the brains of patients with Parkinsonís disease. In our cell studies, we expect to demonstrate that cofilin-1 is involved in the process of oxidative stress, and to show how this occurs. As such, we expect to determine whether cofilin-1 is a suitable new drug target for treating Parkinsonís.
Principal Investigator and Professor at Federal University of Rio Grande do Sul
Location: Porto Alegre (RS), Brazil
Lecturer in Biochemical Toxicology at Kingís College London
Location: London, United Kingdom