Probing for New Targets in Neurological Diseases

Neurodegenerative disorders, such as Alzheimer’s disease, Amyotrophic lateral sclerosis (ALS), Huntington’s disease, and Parkinson’s disease, are among the most devastating diagnoses faced in the clinic today. The progressive loss of neuron structure, function, and vitality characteristic of these diseases generally correlates with progressively poorer quality of living and death in patients. Despite an enormous amount effort, very few therapeutics have been identified that truly cure or even mitigate the symptoms of most neurodegenerative conditions. Although these diseases affect different levels of neuronal circuitry, ranging from molecular to systemic, they share several pathobiological features on the molecular level, including aberrant genetics, protein misfolding, dysfunctional intracellular mechanisms, and premature programmed cell death. By investigating these irregularities, we hope to uncover new therapeutic targets.

Chemical biology approaches to combat Parkinson’s disease and dyskinesia

Our current research is focused on Parkinson’s disease. Treatment options for Parkinson’s disease are currently quite limited, and generally involve dopamine replacement therapy with a variety of dopaminergic agents. Levodopa (L-DOPA), the immediate precursor to dopamine, is currently the gold standard for treatment of Parkinson’s disease. However, L-DOPA therapy leads to undesireable side effects, with approximately 60% of patients experiencing fluctuations in motor performance, psychotic reactions, and levodopa-indused dyskinesias (uncontrolled movements) after just five years or less of treatment. Hence, there is a pressing need for improved antiparkinsonian therapeutics, especially those that could ameliorate the disruptive dyskinesia symptoms. Our lab is leveraging synthetic organic chemistry and biochemical approaches (Felix Nwogbo) to elucidate information about the mechanisms involved in the progression of Parkinson’s disease.