An update on the involvement of inflammatory mediators in Parkinson's disease pathogenesis.

Several endogenous and exogenous mediators and pathogenic agents trigger inflammation. Despite the brain being less vulnerable to inflammation, many studies have underlined the contribution of inflammatory molecules in the pathogenesis of Parkinson's disease (PD). The onset of the features of PD is the result of an interaction of multiple contributors. These factors include inflammatory mediators, α-synuclein accumulation, oxidative stress, mitochondrial dysfunction, and neuronal cell death. Due to multifaceted interaction and cross-talk amongst a bunch of proteins and pathways, deciphering the aetiology of PD has been quite complex and challenging. It is ambiguous whether inflammatory mediators lead to microglial activation and α-synuclein accumulation or vice versa. It is also unclear how inflammatory mediators cross the peripheral nervous system to the brain and trigger dopaminergic cell death. The present review provides an update on the involvement of inflammatory mediators and non-neuronal cells in dopaminergic cell death, which leads to sporadic PD in humans and PD-like features in rodents. The article emphasises the contribution of inflammatory molecules released from the peripheral nervous system in the selective, progressive, and slow demise of nigrostriatal dopaminergic neuronal cells of the midbrain. The article also narrates the challenges and future perspectives.