Parkinson’s Disease (PD) is a highly prevalent neurodegenerative disease among older
adults. PD neuropathology is marked by the progressive loss of the dopaminergic neurons of the
substantia nigra pars compacta and the widespread accumulation of misfolded intracellular
α-synuclein (α-syn). Genetic mutations and post-translational modifications, such as α-syn phosphorylation, have been identified among the multiple factors supporting α-syn accrual during PD.
A decline in the clearance capacity of the ubiquitin-proteasome and the autophagy-lysosomal systems, together with mitochondrial dysfunction, have been indicated as major pathophysiological
mechanisms of PD neurodegeneration. The accrual of misfolded α-syn aggregates into soluble oligomers, and the generation of insoluble fibrils composing the core of intraneuronal Lewy bodies
and Lewy neurites observed during PD neurodegeneration, are ignited by the overproduction of
reactive oxygen species (ROS). The ROS activate the α-syn aggregation cascade and, together with
the Lewy bodies, promote neurodegeneration. However, the molecular pathways underlying the
dynamic evolution of PD remain undeciphered. These gaps in knowledge, together with the clinical heterogeneity of PD, have hampered the identification of the biomarkers that may be used to
assist in diagnosis, treatment monitoring, and prognostication. Herein, we illustrate the main
pathways involved in PD pathogenesis and discuss their possible exploitation for biomarker discovery. CLICK TO REVIEW