Cellular and Molecular Mediators of Neuroinflammation in the Pathogenesis of Parkinson’s Disease

Abstract

Neuroinflammation is a host-defense mechanism associated with restoration of normal structure and function of the brain and neutralization of an insult. Increasing neuropathological and biochemical evidence from the brains of individuals with Parkinson's disease (PD) provides strong evidence for activation of neuroinflammatory pathways. Microglia, the resident innate immune cells, may play a major role in the inflammatory process of the diseased brain of patients with PD. Although microglia forms the first line of defense for the neural parenchyma, uncontrolled activation of microglia may directly affect neurons by releasing various molecular mediators such as inflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-6, and IL-1β), nitric oxide, prostaglandin E2, and reactive oxygen and nitrogen species. Moreover, recent studies have reported that activated microglia phagocytose not only damaged cell debris but also intact neighboring cells. This phenomenon further supports their active participation in self-enduring neuronal damage cycles. As the relationship between PD and neuroinflammation is being studied, there is a realization that both cellular and molecular mediators are most likely assisting pathological processes leading to disease progression. Here, we discuss mediators of neuroinflammation, which are known activators released from damaged parenchyma of the brain and result in neuronal degeneration in patients with PD.

Protective and Toxic Neuroinflammation in Amyotrophic Lateral Sclerosis

“…Once thought to be only a consequence of motor neuron death, neuroinflammation is now established as an important factor not only in the pathogenesis of ALS, but also in many other neurodegenerative diseases, including Parkinson's, Alzheimer's, multiple sclerosis, HIV-associated encephalopathy, and cerebrovascular disease [46][47][48][49][50][51]. Much of what has been learned in ALS regarding neuroinflammation has come through discoveries in these other neurodegenerative diseases.…”

Malathion Neurotoxic Effects on Dopaminergic System in Mice: Role of Inflammation

“…Some studies revealed that one of the mechanisms of dopaminergic degeneration is through neuroinflammatory mediators [30,31]. The proinflammatory cytokines and cells play crucial role in the damage of vulnerable dopaminergic cells.…”

Alterations of p11 in brain tissue and peripheral blood leukocytes in Parkinson’s disease

“…A previous study has shown an increase in infiltrating peripheral cells in the SN of PD patients (31), and PBMC composition and function are reportedly altered in PD patients (32)(33)(34)(35)(36). To ensure that our observed differences in p11 levels were not related to PBMC composition changes, we also quantified leukocyte composition.…”