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.

Highlights

  • Parkinson’s disease (PD), one of the most common neurodegenerative conditions, affects about 2% of older individuals and about 6 million individuals worldwide, and is a progressive nervous system disorder that impairs movement [1]

  • Herpes simplex virus type 1 (HSV-1) seropositivity was higher in PD (98%) than healthy controls (HC) (92%), whereas for the other two herpesviruses an opposite situation was observed as antibodies for both CMV (PD: 88%; HC: 98%) and human herpes virus type 6 (HHV-6) (PD: 56%; HC: 67%) were more frequently observed in HC than in PD patients

  • HSV-1 antibody titers levels were significantly higher in PD compared to HC (p = 0.045)

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Summary

Introduction

Parkinson’s disease (PD), one of the most common neurodegenerative conditions, affects about 2% of older individuals and about 6 million individuals worldwide, and is a progressive nervous system disorder that impairs movement [1]. The most common PD symptoms are resting tremors, unstable posture, bradykinesia, rigidity, and non-motor symptoms, such as dysphagia [2]. PD is characterized by the loss of neurons in the substantia nigra, possibly resulting from the accumulation of misfolded and aggregated forms of α-synuclein protein within Lewy bodies [3,4]. Α-synuclein is a 140 aa protein located at presynaptic terminals. There is no cure for the disease, but dopaminergic therapies as levodopa and dopamine agonists are commonly used for the control of motor symptoms Microglia-driven chronic neuroinflammation, oxidative stress, autophagy disruption, and mitochondrial dysfunction are typical features of the pathology [1,6,7].

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