Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Mar 10;10(3):599.
doi: 10.3390/microorganisms10030599.

Picornavirus May Be Linked to Parkinson's Disease through Viral Antigen in Dopamine-Containing Neurons of Substantia Nigra

Bo Niklasson  1 , Lars Lindquist  2 , William Klitz  3 , Sten Fredrikson  4 , Roland Morgell  1 , Reza Mohammadi  1 , Netherlands Brain Bank  5 , Yervand Karapetyan  6 , Elisabet Englund  7
Affiliations

Picornavirus May Be Linked to Parkinson's Disease through Viral Antigen in Dopamine-Containing Neurons of Substantia Nigra

Bo Niklasson et al. Microorganisms. .

Abstract

Parkinson's disease (PD) is a neurodegenerative disease linked with the loss of dopaminergic neurons in the brain region called substantia nigra and caused by unknown pathogenic mechanisms. Two currently recognized prominent features of PD are an inflammatory response manifested by glial reaction and T-cell infiltration, as well as the presence of various toxic mediators derived from activated glial cells. PD or parkinsonism has been described after infection with several different viruses and it has therefore been hypothesized that a viral infection might play a role in the pathogenesis of the disease. We investigated formalin-fixed post-mortem brain tissue from 9 patients with Parkinson's disease and 11 controls for the presence of Ljungan virus (LV) antigen using a polyclonal antibody against the capsid protein of this recently identified picornavirus with neurotropic properties, suspected of being both a human and an animal pathogen. Evidence of viral antigen was found in 7 out of 9 Parkinson's disease cases and in only 1 out of 11 controls (p = 0.005). The picornavirus antigen was present in dopamine-containing neurons of the substantia nigra. We propose that LV or an LV-related virus initiates the pathological process underlying sporadic PD. LV-related picornavirus antigen has also been reported in patients with Alzheimer's disease. Potentially successful antiviral treatment in Alzheimer's disease suggests a similar treatment for Parkinson's disease. Amantadine, originally developed as an antiviral drug against influenza infection, has also been used for symptomatic treatment of patients with PD for more than 50 years and is still commonly used by neurologists today. The fact that amantadine also has an antiviral effect on picornaviruses opens the question of this drug being re-evaluated as potential PD therapy in combination with other antiviral compounds directed against picornaviruses.

Keywords: Ljungan virus; Parkinson’s disease; immunohistochemistry; neurodegenerative disease; picornavirus; substantia nigra.

PubMed Disclaimer

Conflict of interest statement

The authors have no conflict of interest to report.

Figures

Figure 1
Figure 1
Neuro-melanin-containing neurons in the substantia nigra undergo neurodegeneration during Parkinson’s disease. (A) illustrates an overview of the substantia nigra in a patient with PD while (B–D) are magnifications focusing on one cell indicated by an arrow, staining positive for both neuro-melanin (brown) and LV VP1 (red).
Figure 1
Figure 1
Neuro-melanin-containing neurons in the substantia nigra undergo neurodegeneration during Parkinson’s disease. (A) illustrates an overview of the substantia nigra in a patient with PD while (B–D) are magnifications focusing on one cell indicated by an arrow, staining positive for both neuro-melanin (brown) and LV VP1 (red).
Figure 2
Figure 2
(A,B) illustrate an overview of the substantia nigra from a healthy control patient.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Brettschneider J., Del Tredici K., Lee V.M., Trojanowski J.Q. Spreading of pathology in neurodegenera-tive diseases: A focus on human studies. Nat. Rev. Neurosci. 2015;16:109–120. doi: 10.1038/nrn3887. - DOI - PMC - PubMed
    1. Koo E.H., Lansbury P.T., Jr., Kelly J.W. Amyloid diseases: Abnormal protein aggregation in neurodegeneration. Proc. Natl. Acad. Sci. USA. 1999;96:9989–9990. doi: 10.1073/pnas.96.18.9989. - DOI - PMC - PubMed
    1. Checkoway H., Lundin J.I., Kelada S.N. Neurodegenerative diseases. IARC Sci. Publ. 2011;163:407–419. - PubMed
    1. Bertram L., Tanzi R.E. The genetic epidemiology of neurodegenerative disease. J. Clin. Investig. 2005;115:1449–1457. doi: 10.1172/JCI24761. - DOI - PMC - PubMed
    1. Zhou L., Miranda-Saksena M., Saksena N.K. Viruses and neurodegeneration. Virol. J. 2013;10:172. doi: 10.1186/1743-422X-10-172. - DOI - PMC - PubMed

LinkOut - more resources