Commentary: Progressive inflammation as a contributing factor to early development of Parkinson's disease

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative disorder with three cardinal features of pathology: 1. Aggregation of α-synuclein into intraneuronal structures called Lewy bodies and Lewy neurites. 2. Dysregulated immune activation in the substantia nigra (SN). 3. Degeneration of dopaminergic neurons in the nigrostriatal circuit. The largely correlative nature of evidence in humans has precluded a decisive verdict on the relationship between α-synuclein pathology, inflammation, and neuronal damage. Furthermore, it is unclear whether inflammation plays a role in the early prodromal stages of PD before neuronal damage has occurred and Parkinsonian motor symptoms become apparent. To gain insight into the interaction between the inflammatory response and the development of neuronal pathology in PD, Watson et al. characterized neuroinflammation in a wild-type α-synuclein overexpressing mouse model of prodromal PD. They demonstrate, for the first time, the existence of early and sustained microglial mediated innate inflammation that precedes damage to the nigrostriatal circuit. Additionally they observe the spread of inflammation from the striatum to the SN. This study suggests that early dysregulated inflammation may contribute to progressive nigrostriatal pathology in PD, although the initiating factor that triggers the inflammatory response remains elusive. The novel concept of an early inflammatory response in the development of PD has important implications for preventive and therapeutic strategies for PD.