Insights into Neuroinflammation in Parkinson’s Disease: From Biomarkers to Anti-Inflammatory Based Therapies

Figure 1

Inflammatory pathways in Parkinson’s disease. An acute insult to CNS (e.g., α-synuclein aggregates) triggers the activation of microglia with changes in their morphofunctional characteristics, increased proliferation and release of inflammatory mediators (e.g., cytokines and ROS). Inflammatory molecules can induce the recruitment of peripheral leukocytes into the CNS. This neuroinflammatory process can be regarded as beneficial for neuronal tissue since it promotes clearance of cell debris. Conversely, inflammatory mediators do not modulate only immune cells but also act on neurons, contributing to neurodegeneration. Neuronal death further activates inflammatory mechanisms, resulting in a vicious cycle of inflammation and neuronal death. Systemic inflammation due to infection or peripheral injury can exacerbate symptoms and promote neuronal damage in PD. Leukocytes secrete proinflammatory cytokines which can affect the brain by several routes, including action on endothelial cells and leakage through damaged BBB. These cytokines induce self-synthesis and the synthesis of other cytokines, which can then stimulate microglia to secrete chronically inflammatory mediators, maintaining neuroinflammation and, as a consequence, slow and progressive neuronal death. Genetic and aging factors might contribute to this process. BBB: blood-brain barrier; CNS: central nervous system; PD: Parkinson’s disease, ROS: reactive oxygen species.