Editorial: Parkinson's disease: cell vulnerability and disease progression

The hallmark of Parkinson Disease (PD) is the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc) and the consequent striatal dopamine (DA) deficiency, although it is well recognized that neurodegeneration in PD goes beyond the SNc. Major advances have occurred in recent years on the molecular and pathophysiological basis of PD, however there remain many questions and unknowns regarding SNc cells vulnerability, and the exact significance of Lewy bodies and alpha-synuclein (α-syn) aggregation process regarding disease onset and progression. This Research Topic discuss the etiopathogenesis of PD, presenting a series of papers that provide up-to-date, state-of-the-art information on molecular and cellular mechanisms involved in the neurodegeneration process, neuroimmune pathways, the role of functional and anatomical organization of the basal ganglia as a factor of neuronal vulnerability, the possibility that PD is a prion disease and the cellular response to α-syn aggregation. Understanding the mechanisms underlying vulnerability of dopaminergic midbrain neurons and how pathology becomes widespread are primary objectives of basic and clinical research in PD. Are dopaminergic and other neurons dying by the same pathogenic mechanisms? Do they all die to the same extent or at the same rate? What are the molecular determinants of susceptibility to the disease? To gain insights into these questions, researchers mainly rely in animal models. Blesa and Przedborski (2014) provide a summary of the current knowledge of in vivo models of PD. Whereas PD can be sporadic, genetic or possibly related with toxic/infectious agents, a differential pattern of cell loss among midbrain dopaminergic neurons is observed regardless of disease etiology suggesting that differential dopaminergic neuron vulnerability does not depend on the factor triggering PD " per se " but on intrinsic properties of these specific cell groups. Here, Brichta and Greengard (2014) provides an update review on the molecular basis underlying differential vulnerability of midbrain dopaminergic neurons in PD. For example, for many years many studies have suggested calbindin (CB) as a marker to distinguish between midbrain dopaminergic neurons with different susceptibility to degeneration in PD. Although CB dopaminergic neurons seem to be less prone to MPTP-induced degeneration, Dopeso-Reyes et al. (2014) clearly demonstrated that these neurons are not giving rise to nigro-striatal projections and indeed CB-ir/TH-ir neurons only originate nigro-extrastriatal projections. This data sustain the presence of a potential imbalance between the nigro-striatal and nigroextrastriatal systems in advanced diseases states. Also, Afonso-Oramas et al. (2014) revealed that midbrain dopaminergic axons …