Immune responses in Parkinson's disease: interplay between central and peripheral immune systems

Abstract

The etiology of Parkinson's disease (PD) is complex and most likely involves numerous environmental and heritable risk factors. Recent studies establish that central and peripheral inflammation occurs in the prodromal stage of the disease and sustains disease progression. Aging, heritable risk factors, or environmental exposures may contribute to the initiation of central or peripheral inflammation. One emerging hypothesis is that inflammation plays a critical role in PD neuropathology. Increasing evidence suggest that activation of the peripheral immune system exacerbates the discordant central inflammatory response and synergistically drives neurodegeneration. We provide an overview of current knowledge on the temporal profile of central and peripheral immune responses in PD and discuss the potential synergistic effects of the central and peripheral inflammation in disease development. The understanding of the nature of the chronic inflammation in disease progression and the possible risk factors that contribute to altered central and peripheral immune responses will offer mechanistic insights into PD etiology and pathology and benefit the development of effective tailored therapeutics for human PD.

Figure 1

Interplay between central and peripheral immune systems in Parkinson's disease. The aging process, genetic mutation, and/or dysregulation of certain gene expressions serve as a “priming” stimulus for microglia. Upon secondary stimulation (e.g., environmental toxin, viral infection, high fat diet), peripheral inflammation is induced and communicates with brain through neural (vagal afferent) or humoral routs (e.g., cytokines circulation). The primed microglia are further activated and release excessive quantities of proinflammatory cytokines driving neurodegeneration.