Immune Response Modifications in the Genetic Forms of Parkinson’s Disease: What Do We Know?

Abstract

Parkinson’s disease (PD) is a common neurodegenerative disease characterized by loss of dopaminergic neurons in the pars compacta of the midbrain substantia nigra. PD pathophysiology is complex, multifactorial, and not fully understood yet. Nonetheless, recent data show that immune system hyperactivation with concomitant production of pro-inflammatory cytokines, both in the central nervous system (CNS) and the periphery, is a signature of idiopathic PD. About 5% of PD patients present an early onset with a determined genetic cause, with either autosomal dominant or recessive inheritance. The involvement of immunity in the genetic forms of PD has been a matter of interest in several recent studies. In this review, we will summarize the main findings of this new and promising field of research

Advances in NURR1-Regulated Neuroinflammation Associated with Parkinson’s Disease

“…Excessive neural inflammation is a major contributing factor in neurodegenerative disorders; in PD, the BBB integrity is compromised, which may be preceded by the activation of the innate immune system, permitting the enrollment and stimulation of the adaptive immune mech-inflammation is a major contributing factor in neurodegenerative disorders; in PD, the BBB integrity is compromised, which may be preceded by the activation of the innate immune system, permitting the enrollment and stimulation of the adaptive immune mechanism [20,21]. Deregulation of central and peripheral inflammatory pathways is one of the components of PD pathogenesis [22], which most likely arises due to genetic predispositions in conjunction with immunological changes associated with age and the main activation of glia of neuronal injury (Figure 1).…”

New insight on microglia activation in neurodegenerative diseases and therapeutics

“…Parkinson's disease-associated LRRK2 mutations enhance neuroinflammatory responses, increasing dopaminergic neuron loss and motor deficits. Experiments have shown that the knockdown of the LRRK2 gene in LRRK2 (R1441G) transgenic mice inhibits the conversion of microglia to a proinflammatory phenotype (Magistrelli et al, 2022;Zhang et al, 2022). Microglia-specific regulatory chromatin regions regulate LRRK2 expression in the human frontal cortex and substantiate these results in a human-induced pluripotent stem cell-derived microglia model (Langston et al, 2022).…”

“…The PRKN gene encodes a mutated parkin protein expression inherited in an autosomal recessive manner and is usually an important genetic causative factor in early-onset familial Parkinson's disease (Magistrelli et al, 2022). Loss of function of the parkin protein may cause abnormal mitochondrial Autophagy, and the release of inflammation-associated components in damaged mitochondria leads to activation of NLRP3 inflammatory vesicles and activation of the inflammatory response (Giorgi et al, 2021).…”