Neuronal subpopulations display differential vulnerabilities in neurodegenerative disease. Delineation of underlying fundamental mechanisms will identify new avenues for novel therapies. As altered neuronal Ca2+ homeostasis and metabolic stress represent key features of degenerative diseases, we will elucidate how they lead to neuronal vulnerability in Parkinson's disease (PD), the 2nd most common neurodegenerative disease world wide.
We aim to identify how intrinsic properties, converging signalling mechanisms and key regulatory steps can affect the onset or progression of PD, by comparing vulnerable vs. resistant neurons, molecularly and functionally, in health and disease, in animal models and human disease.
We analyse neuronal subtypes displaying different susceptibility to PD: vulnerable substantia nigra dopamine (SN DA) and locus coeruleus noradrenaline (LC NA) neurons, and resistant / less vulnerable ventral tegmental area (VTA DA) neurons and cholinergic neurons of dorsal motor nucleus of vagus nerve (DMV).