Predavanje prof. dr. Jasona Cannona, School of Health Sciences na Purdue University, održat će se u srijedu 18. rujna 2024. u 13:00 sati u predavaonici O-268, pod naslovom: Inherent dopaminergic neurobiology modulates neurotoxicity.
Abstract: The loss of dopaminergic neurons of the substantia nigra results in many of the cardinal symptoms of Parkinson’s disease (PD). A variety of environmental and genetic risk factors have been linked to PD risk. A key factor in such risk is the inherent neurobiology of dopaminergic neurons that render these cells especially sensitivity to a variety of insults. Numerous classes of chemicals have been found to rather selectively lesion dopaminergic neurons. Using dietary neurotoxicants as models, we have shown that neuromelanin formation modulates neurotoxicity through connections between mitochondrial oxidative stress, respiration deficits, and mitophagy inhibition. Moreover, we have recently identified connections between chemical building blocks of neuromelanin and ferroptosis, a form of cell death due to the failure of antioxidant defense, which leads to the accumulation of phospholipid hydroperoxides to levels resulting in membrane rupture and, ultimately, cell death that is distinct from other forms, such as apoptosis. The three major initiators of this form of cell death are lipids, reactive oxygen species (ROS), and iron. Ongoing studies suggest that these key mechanistic connections and inherent neurobiology intersect to result in selective sensitivity of dopaminergic neurons to a broad range of insults. The elucidation of such primary mechanisms is critical to discover new makers of pathogenesis and new therapeutic targets.