Updates on immunity and inflammation in Parkinson disease pathology

Abstract

Studies in the last decade have suggested the association of both neuroinflammatory processes and immune responses in Parkinson disease (PD) pathology. PD pathology is related to depleted dopamine levels, α-synuclein aggregation, and death of nigrostriatal dopaminergic neurons. Reports have suggested central and peripheral inflammation in the prodromal stage of the disease, which is sustained during disease progression. Alongside the activation of peripheral immune system exacerbates the dissonant central inflammatory responses and could contribute in synergistic neurodegeneration. Activated glial cells contribute significantly in the neuroinflammatory process during the occurrence of the disease and are also acknowledged as a hallmark of disease progression. However, the contribution of glial cells is not well defined in the context of neurodegeneration and neuroprotection. This review provides an overview of the roles of immune and inflammatory responses and their consequences in PD disease pathogenesis and also discusses possible therapeutic strategies for PD based on these findings.

Imbalance of circulating Tfh/Tfr cells in patients with Parkinson’s disease

“…Research on immunity in PD has mostly focused on the activation of microglia and astrocytes, and the imbalance of B lymphocytes and T lymphocytes and their subpopulations [28]. Little research has been carried out to elucidate the role of humoral immunity in PD.…”

The S100B story: from biomarker to active factor in neural injury

“…The disorders considered in the present review are caused by different etiologic factors and display a variety of symptoms that could hardly be reconducted to a unifying pattern. However, regardless of the origin of these diseases, the involvement of processes which share aspects reasonably attributable to inflammation is detectable in their underlying pathogenic mechanisms (Giovannoni et al 2007;Wilcock and Griffin 2013;King et al 2014;Ochoa-Cortes et al 2016;Hamlett et al 2018;Stark et al 2016;Chitnis and Weiner 2017;Labzin et al 2018;Fehily and Fitzgerald 2017;Mizuma and Yenari 2017;Neal and Richardson 2017;Franklin et al 2017;Prata et al 2017;Santos and Ferreira 2017;Joshi and Singh 2017;Thelin et al 2017a;Majd et al 2017;Zhang et al 2017;Zolezzi and Inestrosa 2017). This consideration has also been the object of a recent valuable review (Skaper et al 2018).…”

The Role of Inflammation in Amyloid Diseases

“…In Parkinson's disease (PD), the involvement of inflammation in the disease process is supported by data showing the infiltration of activated microglia and T cells in post-mortem PD brains [81,82] Additionally, there is accumulation of proinflammatory cytokines such as TNF-α, IFN-γ, and IL-6 IL-1β in the brain and cerebrospinal fluid of PD patients [83,84]. The PD culprit protein, α-synuclein, is able to bind to several immune receptors and elicits in vitro and in vivo inflammatory response [85]. Local inflammation has been thoroughly reported for PD patients, mainly derived from activated microglia [82,85].…”

“…The PD culprit protein, α-synuclein, is able to bind to several immune receptors and elicits in vitro and in vivo inflammatory response [85]. Local inflammation has been thoroughly reported for PD patients, mainly derived from activated microglia [82,85]. Protein aggregation in PD extends well beyond the CNS and also affects peripheral autonomic neuronal circuits, such as the enteric nervous system [86].…”