Neuroinflammatory Responses and Parkinson' Disease: Pathogenic Mechanisms and Therapeutic Targets

Parkinson's disease (PD) is the second most common age-related neurodegenerative disorders of the central nervous system, which mainly impairs the motor system. However, the pathogenic mechanisms are still unclear. Gene-environment complex interaction leads to selective dopaminergic neuron death in PD. Growing evidences supports that neuroinflammatory responses are involved in the pathogenesis of PD. This review critically discusses current studies on the inflammatory response of the pathological process of PD. The mechanisms and strategies of modifying inflammatory responses would be potential treatments for neurodegenerative diseases. Graphical abstract Activated microglia canpromote the damage ofdopaminergic neurons, which inturn aggravates the activation ofmicroglia in the process of PD. Atthe same time, microglia canactivate astrocytes throughproliferation and secretion ofinflammatory factors. The role ofastrocytes on the loss ofdopaminergic neurons is stillcontroversial in PD. (Nonsteroidalanti-inflammatory drugs,NSAIDs. adiposed-derived stemcells, ADSCs.nicotinamideadenine dinucleotide phosphate,NADPH. signal transducers andactivators of transcription,STAT.DJ-1,Aliases forPARK7.mesencephalic astrocytederivedneurotrophic factor,MANF.Ciliary neurotrophicfactor,CNTF.glial cell linederivedneurotrophic factor,GDNF.Wnt Family Member1,Wnt1). Graphical abstract Mitochondrial dysfunction causes neuroinflammation throughDAMPs and a series of factors such as oxidative stress andinflammatory bodies in PD. (Damage-associated molecular patterns,DAMPs. reactive oxygen species, ROS). Graphical abstract Various mechanismsparticipate in NLRP3 activation,causing microglia activation inPD. ( -synuclein, -syn.) TolllikeReceptor 2, TLR2. Toll-likeReceptor 4, TLR4. TumorNecrosis Factor, TNF.Apoptosisassociated speck like proteincontaining a CARD, ASC).