Linking Neuroinflammation and Neurodegeneration in Parkinson's Disease

Abstract

Neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD) impose a pressing burden on our developed and consequently aging society. Misfolded protein aggregates are a critical aspect of several neurodegenerative diseases. Nevertheless, several questions remain unanswered regarding the role of misfolded protein aggregates and the cause of neuronal cell death. Recently, it has been postulated that neuroinflammatory processes might play a crucial role in the pathogenesis of PD. Numerous postmortem, brain imaging, epidemiological, and animal studies have documented the involvement of the innate and adaptive immunity in neurodegeneration. Whether these inflammatory processes are directly involved in the etiology of PD or represent secondary consequences of nigrostriatal pathway injury is the subject of intensive research. Immune alterations in response to extracellular α-synuclein may play a critical role in modulating Parkinson's disease progression. In this review, we address the current concept of neuroinflammation and its involvement in PD-associated neurodegeneration.

Figure 1

Overview of clinical and preclinical evidence linking neuroinflammation to neurodegeneration in Parkinson's disease. DN: dopaminergic neurons; TLR: toll-like receptor; STR: striatum; Tg: transgenic; PD: Parkinson's disease; KO: knockout; LBs: Lewy bodies; α-SYN: α-synuclein; NI: neuroinflammation.

Figure 2

Possible link between α-synuclein, neuroinflammatory processes, and neurodegeneration in Parkinson's disease. In the presence of specific α-synuclein conformations, microglia get activated and induce a complex immune response by increasing the expression of toll-like receptors and several proinflammatory mediators, which consequently activates peripheral immune cells like monocytes or T cells. These peripheral immune cells might actively contribute to neurodegeneration.