Role of the Stress-Activated Protein Kinase SPAK/JNK Signaling Pathway in the MPTP-Induced Neuronal Death Model of Parkinsons Disease
Flavell, Richard A., Ph.D.
Dr. Richard A. Flavell will use transgenic mice in his studies of specific enzymes
Progress Report (as of 8/2002)
(Yale University) has been studying excitotoxicity using the neurotransmitter glutamate (found in abundance in the brain) that leads to the activation of a type of cell death known as apoptosis. He and his group created a knock-out mouse model in which a group of proteins (cJun N-terminal Kinase or cJNK) were genetically deleted. These animals are resistant to excitotoxic neuronal damage. They found that they are partially protected against MPTP-induced damage, seen both biochemically and in motor performance. Additional mouse strains were created to more specifically see these neuronal changes, and the group is now seeking to determine if cyclooxygenase-2 (COX-2), a protein earlier identified as neuroinflammatory, has been lessened or possibly abolished in these mice. These results might well be relevant to the pathophysiology of human PD, indicating targets for drug therapy.