The Challenge of the Pathogenesis of Parkinson's Disease: Is Autoimmunity the Culprit?

Abstract

The role of autoimmunity in Parkinson's disease (PD), as one of the most popular research subjects, has been intensively investigated in recent years. Although the ultimate cause of PD is unknown, one major area of interest remains identifying new therapeutic targets and options for patients suffering from PD. Herein, we present a comprehensive review of the impacts of autoimmunity in neurodegenerative diseases, especially PD, and we have composed a logical argument to substantiate that autoimmunity is actively involved in the pathogenesis of PD through several proteins, including α-synuclein, DJ-1, PINK1, and Parkin, as well as immune cells, such as dendritic cells, microglia, T cells, and B cells. Furthermore, a detailed analysis of the relevance of autoimmunity to the clinical symptoms of PD provides strong evidence for the close correlation of autoimmunity with PD. In addition, the previously identified relationships between other autoimmune diseases and PD help us to better understand the disease pattern, laying the foundation for new therapeutic solutions to PD. In summary, this review aims to integrate and present currently available data to clarify the pathogenesis of PD and discuss some controversial but innovative research perspectives on the involvement of autoimmunity in PD, as well as possible novel diagnostic methods and treatments based on autoimmunity targets.

The Functional Roles and Applications of Immunoglobulins in Neurodegenerative Disease

“…Recent clinical evidence shows that autoantibodies play roles in disease; therefore, the concept that neurodegenerative diseases may have an autoimmune etiology has been suggested [ 21 , 22 , 23 ]. Due to recent advances in technology related to antibody screening, many studies are attempting to identify autoantibodies associated with neurodegenerative diseases [ 24 , 25 ].…”

Association between hyperthyroidism and risk of incident in Parkinson’s disease

“…A previous study found that Graves' disease may share genetic pathways with PD and is closely linked to PD's specific clinical manifestations (13). Amplified autoimmune reactions of Graves' disease via shared genetic pathways may also contribute to PD development (14). Third, hyperthyroidism triggers symptoms in patients with subclinical vulnerability to PD by acting on PD's biological substrate.…”

Trained Innate Immunity Not Always Amicable

“…Parkinson’s disease (PD) is an adult onset neurodegenerative disease characterized by selective degeneration of neurons, including loss of dopaminergic neurons and the presence of Lewy bodies containing α-synuclein, which results in motor and nonmotor symptoms [139,140,141]. α-synuclein plays a leading role in the initiation and progression of neurodegeneration as a result of neurotoxicity induction by various pathways, such as inflammation, oxidative stress as well as autophagy abnormalities [141,142]. TLR1 and TLR2 on microglia recognize α-synuclein followed by the activation of phagocytic TAM receptor tyrosine kinases: Axl and Mer [143].…”