Neuroinflammation in Parkinson's disease: a target for neuroprotection?
Parkinson's disease is characterised by a slow and progressive degeneration of dopaminergic neurons in the substantia nigra. Despite intensive research, the cause of the neuronal loss in Parkinson's disease is poorly understood. Neuroinflammatory mechanisms might contribute to the cascade of events leading to neuronal degeneration. In this Review, we describe the evidence for neuroinflammatory processes from post-mortem and in vivo studies in Parkinson's disease. We further identify the cellular and molecular events associated with neuroinflammation that are involved in the degeneration of dopaminergic neurons in animal models of the disease. Overall, available data support the importance of non-cell-autonomous pathological mechanisms in Parkinson's disease, which are mostly mediated by activated glial and peripheral immune cells. This cellular response to neurodegeneration triggers deleterious events (eg, oxidative stress and cytokine-receptor-mediated apoptosis), which might eventually lead to dopaminergic cell death and hence disease progression. Finally, we highlight possible therapeutic strategies (including immunomodulatory drugs and therapeutic immunisation) aimed at downregulating these inflammatory processes that might be important to slow the progression of Parkinson's disease.
Hirsch
Etienne C
EC
INSERM, UMRS 975, Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière, Experimental Therapeutics of Neurodegeneration, Paris, France. etienne.hirsch@upmc.fr
Hunot
Stéphane
S
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D016923:Cell Death / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D007114:Immunization; D007155:Immunologic Factors / Q000627:therapeutic use; D007249:Inflammation / Q000473:pathology* / Q000503:physiopathology*; D009410:Nerve Degeneration / Q000503:physiopathology / Q000628:therapy; D015213:Neuroimmunomodulation; D009474:Neurons / Q000502:physiology; D018696:Neuroprotective Agents / Q000627:therapeutic use; D010300:Parkinson Disease / Q000473:pathology* / Q000503:physiopathology* / Q000628:therapy
D000893:Anti-Inflammatory Agents; D007155:Immunologic Factors; D018696:Neuroprotective Agents; D004298:Dopamine