Immunogenetic Determinants of Parkinson’s Disease Etiology

Abstract

Parkinson’s disease (PD) is increasingly recognised as a systemic disorder in which inflammation might play a causative role rather than being a consequence or an epiphenomenon of the neurodegenerative process. Although growing genetic evidence links the central and peripheral immune system with both monogenic and sporadic PD, our understanding on how the immune system contributes to PD pathogenesis remains a daunting challenge. In this review, we discuss recent literature aimed at exploring the role of known genes and susceptibility loci to PD pathogenesis through immune system related mechanisms. Furthermore, we outline shared genetic etiologies and interrelations between PD and autoimmune diseases and underlining challenges and limitations faced in the translation of relevant allelic and regulatory risk loci to immune-pathological mechanisms. Lastly, with the field of immunogenetics expanding rapidly, we place these insights into a future context highlighting the prospect of immune modulation as a promising disease-modifying strategy.

Towards a Global View of Parkinson's Disease Genetics

“…[33][34][35] Recent genetic studies have begun to yield important insights into overlapping genetic etiologies between PD and a number of other conditions. 7,[36][37][38] Although the genetics of these conditions are known to vary between different ancestral populations, [39][40][41] little is known about potential shared pleiotropic intricacies. This further underscores the importance of understanding the global architecture of PD, as pleiotropic loci may facilitate the discovery of the etiology and epidemiology of related diseases with shared genetic risk factors.…”

“…Recent genetic studies have begun to yield important insights into overlapping genetic etiologies between PD and a number of other conditions 7,36–38 . Although the genetics of these conditions are known to vary between different ancestral populations, 39–41 little is known about potential shared pleiotropic intricacies.…”

Novel diagnostic biomarkers related to immune infiltration in Parkinson’s disease by bioinformatics analysis

“…Recent studies have elucidated that dysregulated expression of miRNAs plays a substantial role in regulating PD ( Briggs et al, 2015 ; Nair and Ge, 2016 ). For instance, miR-153 can significantly reduce expression of synuclein-alpha (SNCA) ( Je and Kim, 2017 ), which has been confirmed to be relevant to the pathogenesis of PD ( Lesage et al, 2020 ; Kung et al, 2022 ). Moreover, miRNAs are not only related to dopaminergic neuron survival ( Kabaria et al, 2015 ) and neuroinflammation ( Yao et al, 2018 ), but can also serve as diagnostic biomarkers ( Shu et al, 2020 ) and therapeutic tools for PD ( Gan et al, 2019 ; Nies et al, 2021 ).…”

Linking Immune Activation and Parkinson’s Disease

“…PD is influenced by many factors including a mix of immunogenetics and the environment, such as infection history. In recent years, increasing evidence suggests an association with autoimmune conditions, with the involvement of the immune system or its aberrant responses in patients and various experimental models [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. In this special issue, our authors highlight the latest research breakthroughs on the links between immune activation and neuroinflammation and PD, and discuss the challenges and novel therapeutic strategies targeting the immune system ISSN 1877-7171/$35.00 © 2022 -IOS Press.…”

“…In summary, multiple independent studies in clinical and pre-clinical models have provided corroborative evidence of the involvement of central and peripheral immune and inflammatory processes in PD [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. Our knowledge of how the immune system contributes to PD pathogenesis is constantly evolving with increasing evidence for a role of several genes and susceptibility loci [1,2].…”