Neuroinflammation in Parkinson's disease: its role in neuronal death and implications for therapeutic intervention.

摘要: Parkinson's disease (PD) is the second most common neurodegenerative disease, after Alzheimer's disease. The potential causes of PD remain uncertain, but recent studies suggest neuroinflammation and microglia activation play important roles in pathogenesis. Major unanswered questions include whether protein aggregates cause selective loss dopaminergic neurons substantia nigra that underlies clinical symptoms a consequence or nigral cell loss. Within microenvironment brain, glial cells critical role homeostatic mechanisms promote neuronal survival. Microglia have specialized immune surveillance mediate innate responses to invading pathogens by secreting myriad factors include, cytokines, chemokines, prostaglandins, reactive oxygen nitrogen species, growth factors. Some these neuroprotective trophic activities aid brain repair processes; while others enhance oxidative stress trigger apoptotic cascades neurons. Therefore, pro- anti-inflammatory must be balance prevent detrimental effects prolonged unregulated inflammation-induced on vulnerable populations. In this review, we discuss triggers review strongest direct evidence chronic may more versus other diseases. Alternatively, propose genetic deficiency not only way reduce protective which function keep microglial check regulate sensitivity DA If inflammation can shown decrease levels midbrain, essence haploinsufficiency such as Parkin RGS10 result from purely environmental (aging, systemic etc.), increasing vulnerability neuron death predisposing an individual development PD. Lastly, latest epidemiological experimental supporting use immunomodulatory drugs agents delay progressive nigrostriatal degeneration leads motor dysfunction