Physical Activity in Patients With Parkinson's Disease: a "Disease Modifying" Intervention?

Parkinson's disease (PD) is a neurodegenerative disease characterized by bradykinesia, rigors, and tremor at rest. Distinctive neuropathological signs include progressive loss of dopaminergic neurons in the Substantia nigra pars compacta (SNpc) and the presence of immunoreactive protein inclusions for α-syn, Lewy bodies (LB). The clinical phenotype is heterogeneous, both from a motor and non-motor point of view. Furthermore, the prognosis and response to drugs are highly variable and poorly predictable. To date, there are no biomarkers capable of early identification of clinical phenotypes and of predicting response to therapy. This constitutes a serious limit that probably represents one of the causes of the failure of the experimentation of the disease modifying therapies tested up to now (for example the anti-α-sin antibodies). Certainly, a deeper understanding of disease pathogenesis is needed to address these unsolved problems. Oxidative stress and inflammation have critical roles in PD, especially in the prodromal and early stages of PD, as they contribute to pathological progression and also trigger potentially devastating neuroprotective responses, especially in the early stages. Consequently, soluble mediators of these processes may represent potential markers of prodromal phases of the disease. Inflammation is a key factor in the initiation and propagation of a-syn aggregates and the contribution of microglial activation to a-syn pathology has been highlighted recently. Elevated a-syn specific T cell responses may be present years before the diagnosis of motor PD, suggesting a role of neuroinflammation in PD pathogenesis and early diagnosis. Furthermore, studies in rats overexpressing a-syn support the idea that reducing neuroinflammation could improve symptoms in early Parkinson's disease. In particular, drug-targeted anti-inflammatory approaches in a-syn rats prevent central and peripheral inflammation, as well as neuronal dysfunction and motor motor i