Abstract: Parkinson’s disease (PD) is a heterogeneous multifactorial disorder and, during the last years, new scientific evidence has supported this concept. The principal hallmarks of PD are the loss of dopaminergic neurons in the substantia nigra pars compacta and the aggregation of misfolded alpha-synuclein (α-syn). In particular, α-syn is receiving great attention for its key role in PD neuropathology. Both genetic mutations and post-translational modifications (i.e., α-syn phosphorylation) can induce protein misfolding. An abnormal accumulation of this misfolded α-syn crushes both the ubiquitin-proteosome and autophagy systems, which are involved in protein clearance. As a result, α-syn aggregation leads to neuronal dysfunction and neurodegeneration. Along with this pathological condition, dysregulated mitochondrial activity, reactive oxygen species production, oxidative stress, and blood-brain barrier alteration, are typical features of neurological disorders such as PD. In addition, neuroinflammatory processes are critical for PD pathogenesis and strictly interconnected to α-syn pathology. According to this, neuroinflammation could be considered as a potential early drug target.