Genetic and Environmental Factors in Parkinson's Disease Converge on Immune Function and Inflammation

Elizabeth M. Kline; Madelyn C. Houser; Mary K. Herrick; Philip Seibler; Christine Klein; Andrew West; Malú G. Tansey

doi:10.1002/mds.28411

Genetic and Environmental Factors in Parkinson's Disease Converge on Immune Function and Inflammation

Elizabeth M. Kline, Madelyn C. Houser, Mary K. Herrick, Philip Seibler, Christine Klein, Andrew West, Malú G. Tansey^*

^*Corresponding author for this work

113 Citations (Scopus)

Abstract

Idiopathic Parkinson's disease (iPD) is a movement disorder characterized by the degeneration of dopaminergic neurons and aggregation of the protein α-synuclein. Patients with iPD vary in age of symptom onset, rate of progression, severity of motor and non-motor symptoms, and extent of central and peripheral inflammation. Genetic and environmental factors are believed to act synergistically in iPD pathogenesis. We propose that environmental factors (pesticides and infections) increase the risk for iPD via the immune system and that the role of PD risk genes in immune cells is worthy of investigation. This review highlights the major PD-relevant genes expressed in immune cells and key environmental factors that activate immune cells and, alone or in combination with other factors, may contribute to iPD pathogenesis. By reviewing these interactions, we seek to enable the future development of immunomodulatory approaches to prevent or delay onset of iPD.

Original language	English
Journal	Movement Disorders
Volume	36
Issue number	1
Pages (from-to)	25-36
Number of pages	12
ISSN	0885-3185
DOIs	https://doi.org/10.1002/mds.28411
Publication status	Published - 01.2021

Funding

Funding for the authors was partially derived from the Michael J. Fox Foundation for Parkinson's Research; the Parkinson's Foundation; Emory University School of Medicine Movement Disorders Center; Udall Center for Excellence in Parkinson's Research; and the National Institutes of Health 1R01NS092122, 1RF1AG051514, 1RF1AG057247 (M.G.T.), T32‐GM08605 (M.K.H. and E.M.K.), 1R01NS064934, P50NS108675, and R33NS097643 (A.B.W.) and from the DFG (Cluster of Excellence, Precision Medicine in Chronic Inflammation and FOR 2488) (P.S. and C.K.). Funding agencies: Michael J. Fox Foundation for Parkinson's Research LRRK2 in Immunity National Institute of General Medical Sciences T32-GM08605 National Institute of Neurological Disorders and Stroke 1R01NS064934 1R01NS092122 P50NS108675 R33NS097643 National Institute on Aging 1RF1AG051514 1RF1AG057247 Parkinson's Foundation Research Center of Excellence.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Areas and Centers

Research Area: Medical Genetics
Academic Focus: Center for Infection and Inflammation Research (ZIEL)

DFG Research Classification Scheme

2.23-06 Molecular and Cellular Neurology and Neuropathology
2.21-05 Immunology

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10.1002/mds.28411

Cite this

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title = "Genetic and Environmental Factors in Parkinson's Disease Converge on Immune Function and Inflammation",

abstract = "Idiopathic Parkinson's disease (iPD) is a movement disorder characterized by the degeneration of dopaminergic neurons and aggregation of the protein α-synuclein. Patients with iPD vary in age of symptom onset, rate of progression, severity of motor and non-motor symptoms, and extent of central and peripheral inflammation. Genetic and environmental factors are believed to act synergistically in iPD pathogenesis. We propose that environmental factors (pesticides and infections) increase the risk for iPD via the immune system and that the role of PD risk genes in immune cells is worthy of investigation. This review highlights the major PD-relevant genes expressed in immune cells and key environmental factors that activate immune cells and, alone or in combination with other factors, may contribute to iPD pathogenesis. By reviewing these interactions, we seek to enable the future development of immunomodulatory approaches to prevent or delay onset of iPD.",

author = "Kline, \{Elizabeth M.\} and Houser, \{Madelyn C.\} and Herrick, \{Mary K.\} and Philip Seibler and Christine Klein and Andrew West and Tansey, \{Mal{\'u} G.\}",

note = "Publisher Copyright: {\textcopyright} 2020 International Parkinson and Movement Disorder Society",

year = "2021",

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T1 - Genetic and Environmental Factors in Parkinson's Disease Converge on Immune Function and Inflammation

AU - Kline, Elizabeth M.

AU - Houser, Madelyn C.

AU - Herrick, Mary K.

AU - Seibler, Philip

AU - Klein, Christine

AU - West, Andrew

AU - Tansey, Malú G.

PY - 2021/1

Y1 - 2021/1

N2 - Idiopathic Parkinson's disease (iPD) is a movement disorder characterized by the degeneration of dopaminergic neurons and aggregation of the protein α-synuclein. Patients with iPD vary in age of symptom onset, rate of progression, severity of motor and non-motor symptoms, and extent of central and peripheral inflammation. Genetic and environmental factors are believed to act synergistically in iPD pathogenesis. We propose that environmental factors (pesticides and infections) increase the risk for iPD via the immune system and that the role of PD risk genes in immune cells is worthy of investigation. This review highlights the major PD-relevant genes expressed in immune cells and key environmental factors that activate immune cells and, alone or in combination with other factors, may contribute to iPD pathogenesis. By reviewing these interactions, we seek to enable the future development of immunomodulatory approaches to prevent or delay onset of iPD.

AB - Idiopathic Parkinson's disease (iPD) is a movement disorder characterized by the degeneration of dopaminergic neurons and aggregation of the protein α-synuclein. Patients with iPD vary in age of symptom onset, rate of progression, severity of motor and non-motor symptoms, and extent of central and peripheral inflammation. Genetic and environmental factors are believed to act synergistically in iPD pathogenesis. We propose that environmental factors (pesticides and infections) increase the risk for iPD via the immune system and that the role of PD risk genes in immune cells is worthy of investigation. This review highlights the major PD-relevant genes expressed in immune cells and key environmental factors that activate immune cells and, alone or in combination with other factors, may contribute to iPD pathogenesis. By reviewing these interactions, we seek to enable the future development of immunomodulatory approaches to prevent or delay onset of iPD.

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M3 - Scientific review articles

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AN - SCOPUS:85097489035

SN - 0885-3185

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Genetic and Environmental Factors in Parkinson's Disease Converge on Immune Function and Inflammation

Abstract

Funding

UN SDGs

Research Areas and Centers

DFG Research Classification Scheme

Access to Document

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