Determinants Of Selective Vulnerability Of Dopamine Neurons In Parkinson'S Disease

Parkinsonu0027s disease (PD) shows regionally selective neuropathology, and several mechanisms have been proposed to explain what makes a few neuronal populations particularly vulnerable to the disease. This review discusses the main hypotheses for this selective vulnerability with a focus on dopamine (DA) neurons in the substantia nigra pars compacta, whose loss determines the main motor symptoms of PD: their neurotransmitter, DA, itself; their morphology, especially their long and highly branched axon; and their physiological phenotype coupled to a large influx of Ca 2+ due to CaV1.3 channels engaging in their pacemaker activity. Interestingly, all these mechanisms seem to converge on mitochondria dysfunction, as it will be described. Understanding the causes of this specific vulnerability is the key to design better therapeutic strategies against the disease.