EOHSI/NIEHS Seminar Series – Fall 2015
Eunsook Lee, R.Ph., Ph.D.
Department of Physiology, Meharry Medical College
“Astrocytic glutamate transporters as potential drug targets to treat neurodegenerative diseases: Mechanism of manganese (Mn)-induced neurotoxicity via astrocytic glutamate transporters”
September 17, 2015 – 12:00 PM
Rutgers University – Busch Campus
EOHSI – Conference Room C
170 Frelinghuysen Road, Piscataway NJ 08854
Summary: Parkinson’s disease (PD) is a neurodegenerative disease which can be ascribed in only 10-20% of cases to genetics. Epidemiological evidence suggests that PD is associated with the use of pesticides, herbicides and heavy metals, including manganese (Mn). Chronic exposure to high Mn levels causes manganism, which has shared features with PD, but the mechanisms by which Mn induces neurotoxicity have yet to be fully established. Mn decreases expression of astrocytic glutamate transporters (GLT-1 and GLAST), which regulates synaptic glutamate levels and prevents excitotoxic neuronal injury.
We have found that the transcription factor yin yang 1 (YY1) plays a critical role in the effect of Mn on GLT-1 and GLAST. Accordingly, delineating the precise mechanism of Mn-induced dysregulation of GLT-1/GLAST expression is critical in advancing our understanding of Mn neurotoxicity. Moreover, identifying molecular targets of Mn-induced GLT-1/GLAST dysfunction will have broad applicability, since a plethora of neurodegenerative diseases, such as PD, Alzheimer’s disease and amyotrophic lateral sclerosis are associated with perturbed glutamate homeostasis secondary to GLT-1/GLAST dysfunction. Thus, our long-term goal is to understand the mechanisms involved in the regulation of GLT-1/GLAST expression in relation to the excitotoxic neurodegeneration.
In the seminar, I would like to share some of our findings how YY1 regulates Mn-induced repression of GLT-1.