Experimental Models to Study Immune Dysfunction in the Pathogenesis of Parkinson's Disease

doi:10.3390/ijms25084330

Review

. 2024 Apr 14;25(8):4330.

doi: 10.3390/ijms25084330.

Experimental Models to Study Immune Dysfunction in the Pathogenesis of Parkinson's Disease

Jasna Saponjic¹, Rebeca Mejías^{2

3}, Neda Nikolovski⁴, Milorad Dragic^{5

6}, Asuman Canak⁷, Stamatia Papoutsopoulou⁸, Yasemin Gürsoy-Özdemir⁹, Kari E Fladmark¹⁰, Panagiotis Ntavaroukas⁸, Nuray Bayar Muluk¹¹, Milica Zeljkovic Jovanovic⁵, Ángela Fontán-Lozano^{2

3}, Cristoforo Comi¹², Franca Marino¹³

Affiliations

¹ Department of Neurobiology, Institute of Biological Research "Sinisa Stankovic", National Institute of the Republic of Serbia, University of Belgrade, 11108 Belgrade, Serbia.
² Department of Physiology, School of Biology, University of Seville, 41012 Seville, Spain.
³ Instituto de Biomedicina de Sevilla, IBiS, Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, 41013 Seville, Spain.
⁴ Department of Immunology, Institute for Biological Research "Siniša Stanković", National Institute of the Republic of Serbia, University of Belgrade, 11108 Belgrade, Serbia.
⁵ Laboratory for Neurobiology, Department for General Physiology and Biophysics, Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia.
⁶ Department of Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences-National Institute of the Republic of Serbia, University of Belgrade, 11351 Belgrade, Serbia.
⁷ Department of Medical Services and Techniques, Vocational School of Health Services, Recep Tayyip Erdogan University, Rize 53100, Turkey.
⁸ Department of Biochemistry and Biotechnology, Faculty of Health Sciences, University of Thessaly, Biopolis, 41500 Larisa, Greece.
⁹ Department of Neurology, School of Medicine, Koç University, Istanbul 34010, Turkey.
¹⁰ Department of Biological Science, University of Bergen, 5020 Bergen, Norway.
¹¹ Department of Otorhinolaryngology, Faculty of Medicine, Kirikkale University, Kirikkale 71450, Turkey.
¹² Neurology Unit, Department of Translational Medicine, S. Andrea Hospital, University of Piemonte Orientale, 13100 Vercelli, Italy.
¹³ Center for Research in Medical Pharmacology, School of Medicine, University of Insubria, 21100 Varese, Italy.

PMID: 38673915
PMCID: PMC11050170
DOI: 10.3390/ijms25084330

Review

Experimental Models to Study Immune Dysfunction in the Pathogenesis of Parkinson's Disease

Jasna Saponjic et al. Int J Mol Sci. 2024.

. 2024 Apr 14;25(8):4330.

doi: 10.3390/ijms25084330.

Authors

Affiliations

¹ Department of Neurobiology, Institute of Biological Research "Sinisa Stankovic", National Institute of the Republic of Serbia, University of Belgrade, 11108 Belgrade, Serbia.
² Department of Physiology, School of Biology, University of Seville, 41012 Seville, Spain.
³ Instituto de Biomedicina de Sevilla, IBiS, Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, 41013 Seville, Spain.
⁴ Department of Immunology, Institute for Biological Research "Siniša Stanković", National Institute of the Republic of Serbia, University of Belgrade, 11108 Belgrade, Serbia.
⁵ Laboratory for Neurobiology, Department for General Physiology and Biophysics, Faculty of Biology, University of Belgrade, 11000 Belgrade, Serbia.
⁶ Department of Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences-National Institute of the Republic of Serbia, University of Belgrade, 11351 Belgrade, Serbia.
⁷ Department of Medical Services and Techniques, Vocational School of Health Services, Recep Tayyip Erdogan University, Rize 53100, Turkey.
⁸ Department of Biochemistry and Biotechnology, Faculty of Health Sciences, University of Thessaly, Biopolis, 41500 Larisa, Greece.
⁹ Department of Neurology, School of Medicine, Koç University, Istanbul 34010, Turkey.
¹⁰ Department of Biological Science, University of Bergen, 5020 Bergen, Norway.
¹¹ Department of Otorhinolaryngology, Faculty of Medicine, Kirikkale University, Kirikkale 71450, Turkey.
¹² Neurology Unit, Department of Translational Medicine, S. Andrea Hospital, University of Piemonte Orientale, 13100 Vercelli, Italy.
¹³ Center for Research in Medical Pharmacology, School of Medicine, University of Insubria, 21100 Varese, Italy.

PMID: 38673915
PMCID: PMC11050170
DOI: 10.3390/ijms25084330

Abstract

Parkinson's disease (PD) is a chronic, age-related, progressive multisystem disease associated with neuroinflammation and immune dysfunction. This review discusses the methodological approaches used to study the changes in central and peripheral immunity in PD, the advantages and limitations of the techniques, and their applicability to humans. Although a single animal model cannot replicate all pathological features of the human disease, neuroinflammation is present in most animal models of PD and plays a critical role in understanding the involvement of the immune system (IS) in the pathogenesis of PD. The IS and its interactions with different cell types in the central nervous system (CNS) play an important role in the pathogenesis of PD. Even though culture models do not fully reflect the complexity of disease progression, they are limited in their ability to mimic long-term effects and need validation through in vivo studies. They are an indispensable tool for understanding the interplay between the IS and the pathogenesis of this disease. Understanding the immune-mediated mechanisms may lead to potential therapeutic targets for the treatment of PD. We believe that the development of methodological guidelines for experiments with animal models and PD patients is crucial to ensure the validity and consistency of the results.

Keywords: Parkinson’s disease; animal models; cellular models; immune systems; neurodegeneration; neuroinflammation; peripheral immune cells.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

**Figure 1**
Schematic summary of the animal models of PD to study the immune system.

**Figure 2**
Peripheral and central immunity in the pathogenesis of PD.

See this image and copyright information in PMC

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[1] Elbaz A., Carcaillon L., Kab S., Moisan F. Epidemiology of Parkinson’s Disease. Rev. Neurol. 2016;172:14–26. doi: 10.1016/j.neurol.2015.09.012. - DOI - PubMed

[2] Elbaz A., Carcaillon L., Kab S., Moisan F. Epidemiology of Parkinson’s Disease. Rev. Neurol. 2016;172:14–26. doi: 10.1016/j.neurol.2015.09.012. - DOI - PubMed

[3] Savica R., Grossardt B.R., Bower J.H., Ahlskog J.E., Rocca W.A. Time Trends in the Incidence of Parkinson Disease. JAMA Neurol. 2016;73:981. doi: 10.1001/jamaneurol.2016.0947. - DOI - PMC - PubMed

[4] Savica R., Grossardt B.R., Bower J.H., Ahlskog J.E., Rocca W.A. Time Trends in the Incidence of Parkinson Disease. JAMA Neurol. 2016;73:981. doi: 10.1001/jamaneurol.2016.0947. - DOI - PMC - PubMed

[5] Feigin V.L., Nichols E., Alam T., Bannick M.S., Beghi E., Blake N., Culpepper W.J., Dorsey E.R., Elbaz A., Ellenbogen R.G., et al. Global, Regional, and National Burden of Neurological Disorders, 1990–2016: A Systematic Analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019;18:459–480. doi: 10.1016/S1474-4422(18)30499-X. - DOI - PMC - PubMed

[6] Feigin V.L., Nichols E., Alam T., Bannick M.S., Beghi E., Blake N., Culpepper W.J., Dorsey E.R., Elbaz A., Ellenbogen R.G., et al. Global, Regional, and National Burden of Neurological Disorders, 1990–2016: A Systematic Analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019;18:459–480. doi: 10.1016/S1474-4422(18)30499-X. - DOI - PMC - PubMed

[7] Terkelsen M.H., Klaestrup I.H., Hvingelby V., Lauritsen J., Pavese N., Romero-Ramos M. Neuroinflammation and Immune Changes in Prodromal Parkinson’s Disease and Other Synucleinopathies. J. Park. Dis. 2022;12:S149–S163. doi: 10.3233/JPD-223245. - DOI - PMC - PubMed

[8] Terkelsen M.H., Klaestrup I.H., Hvingelby V., Lauritsen J., Pavese N., Romero-Ramos M. Neuroinflammation and Immune Changes in Prodromal Parkinson’s Disease and Other Synucleinopathies. J. Park. Dis. 2022;12:S149–S163. doi: 10.3233/JPD-223245. - DOI - PMC - PubMed

[9] Tansey M.G., Wallings R.L., Houser M.C., Herrick M.K., Keating C.E., Joers V. Inflammation and Immune Dysfunction in Parkinson Disease. Nat. Rev. Immunol. 2022;22:657. doi: 10.1038/s41577-022-00684-6. - DOI - PMC - PubMed

[10] Tansey M.G., Wallings R.L., Houser M.C., Herrick M.K., Keating C.E., Joers V. Inflammation and Immune Dysfunction in Parkinson Disease. Nat. Rev. Immunol. 2022;22:657. doi: 10.1038/s41577-022-00684-6. - DOI - PMC - PubMed

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Experimental Models to Study Immune Dysfunction in the Pathogenesis of Parkinson's Disease

Affiliations

Experimental Models to Study Immune Dysfunction in the Pathogenesis of Parkinson's Disease

Authors

Affiliations

Abstract

Conflict of interest statement

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Abstract

Conflict of interest statement

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