A Possible Role for HSV-1-Specific Humoral Response and PILRA rs1859788 Polymorphism in the Pathogenesis of Parkinson’s Disease

Abstract

The etiology of Parkinson’s disease (PD), a progressive nervous system disorder that affects movement, is still unknown; both genetic and environmental factor are believed to be involved in onset of the disease and its development. Herpes simplex virus type 1 (HSV-1), in particular, is suspected to have a role in PD. Paired Immunoglobulin-like type 2 receptor alpha (PILRA) is an inhibitory receptor that down-regulates inflammation and is expressed on innate immune cells. The PILRA rs1859788 polymorphism is protective against Alzheimer’s disease, even in relation with HSV-1 antibody titers, but no data are available in PD. We analyzed HSV-1 antibody titers and PILRA rs1859788 in PD (n = 51) and age-and sex-matched healthy controls (HC; n = 73). Results showed that HSV-1, but not cytomegalovirus (CMV) or human herpes virus type 6 (HHV-6) antibody titers were significantly higher in PD compared to HC (p = 0.045). The rs1859788 polymorphism was not differentially distributed between PD and HC, but the minor allele A was more frequently carried by PD (68%) compared to HC (50%) (p = 0.06). Notably, the rs1859788 minor allele A was statically more frequent in male PD (65%) compared to male HC (37%) (p = 0.036). Finally, no relation was found between HSV-1 antibody titers and PILRA genotype. Results herein suggest an involvement of HSV-1 in PD and indicate a possible interaction between PILRA gene polymorphisms and this neuropathology.

Antibodies against HSV-1 and Curli Show the Highest Correlation in Parkinson’s Disease Patients in Comparison to Healthy Controls

“…It also seems that accurate oral and dental hygiene in Parkinson’s patients can be effective in prevention and reduction the symptoms of the disease. We observed a statistically significant difference in antibody levels against a common pathogen of the central nervous system, HSV-1 (Ul42 22–36 ) in PD patients in comparison to HCs [ 9 ], which was consistent with other studies [ 34 ]. Furthermore, the antibodies able to recognize the HSV-1-Ul42 22–36 peptide are able to cross-react with the homologous human α-syn 100–114 epitope [ 9 ].…”

Serum and Exosomal miR-7-1-5p and miR-223-3p as Possible Biomarkers for Parkinson’s Disease

“…Soluble total α-Syn (ng/mL) was measured in the serum of all the enrolled subjects via commercial Enzyme-Linked ImmunoSorbent Assays (ELISA) according to the manufacturer's instructions (IBL International, Hamburg, Germany) [27].…”

Systemic immune challenge exacerbates neurodegeneration in a model of neurological lysosomal disease

“…In this regard, it is believed that chronic bacterial and viral infections contribute to the progression of several other brain diseases (Perry et al, 2007 ). Notably, there is evidence linking herpes simplex type 1 (HSV-1) infections with increased risk of Alzheimer’s disease (AD)-like pathology development (Eimer et al, 2018 ), as well as chronic Parkinson-like symptoms (Caggiu et al, 2016 , 2017 ; Agostini et al, 2021 ), Influenza-A virus (IAV), which also appears to be linked to Parkinson disease onset, was proved to cause cognitive decline and hippocampal morphological changes, when injected into the olfactory bulb of BALB/c mice (Furlan Damiano et al, 2022 ). In addition, changes in brain structure have also recently been reported in SARS-CoV-2 cases, where reduction in grey matter thickness and changes in markers of tissue damage were observed in regions that are functionally connected to the primary olfactory cortex (Douaud et al, 2022 ).…”