Funded Studies
Understanding the mechanism of the disease process of Parkinson's dis and development of effective neuroprotective therapeutic approach to halt the disease progression are of paramount importance. It is believed that complex interaction between environmental and genetic factors leads to activation of certain brain cells and induction of broad-spectrum inflammatory reactions followed by degeneration of dopamine-synthesizing neurons in the midbrain.
Expression of different inflammatory and proinflammatory molecules depends on the activation of a transcription factor called nuclear factor-kappaB (NF-kB). Apart from its involvement in inflammation, activation of NF-kB is also involved in several physiological processes. It has been shown that peptides corresponding to the NF-kB essential modifier (NEMO)-binding domain (NBD) of IkB kinase (IKK)a or IKKb specifically inhibit the induction of NF-kB activation without inhibiting the basal NF-kB activity.
Recently we have found that NBD peptides markedly inhibit the neuroinflammatory disease process of multiple sclerosis (MS) in animals and attenuate the expression of proinflammatory molecules in a CNS inflammatory model. These results raise the possibility that NBD peptides may turn out to be an anti-neuroinflammatory drug. Unlike MS, PD is not an autoimmune disorder. However, similar to MS, inflammation within the CNS plays a major role in the loss of dopaminergic neurons in PD patients.
The MPTP pre-clinical model has become particularly useful for testing potential therapeutic agents against PD. Therefore, it is worth testing whether specific inhibition of induced NF-kB activation by NBD peptides attenuate the loss of dopaminergic neurons in this model. A positive outcome from this project will enhance the possibility of treating PD patients with NBD peptides as primary or adjunct therapy.