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

被引：74

作者：

Kline, Elizabeth M. ^{[1
,2
]}

Houser, Madelyn C. ^{[1
,3
]}

Herrick, Mary K. ^{[1
,4
,5
]}

Seibler, Philip ^{[6
]}

Klein, Christine ^{[6
]}

West, Andrew ^{[7
]}

Tansey, Malu G. ^{[4
,5
]}

机构：

[1] Emory Univ, Laney Grad Sch, Atlanta, GA 30322 USA

[2] Univ Connecticut, Dept Mol & Cell Biol, Storrs, CT USA

[3] Emory Univ, Sch Nursing, Atlanta, GA 30322 USA

[4] Univ Florida, Coll Med, Dept Neurosci, Ctr Translat Res Neurodegenerat Dis, Gainesville, FL 32610 USA

[5] Univ Florida, Coll Med, Dept Neurol, Ctr Translat Res Neurodegenerat Dis, Gainesville, FL 32610 USA

[6] Univ Lubeck, Inst Neurogenet, Lubeck, Germany

[7] Duke Univ, Duke Ctr Neurodegenerat & Neurotherapeut, Durham, NC USA

来源：

MOVEMENT DISORDERS | 2021年 / 36卷 / 01期

基金：

美国国家卫生研究院;

关键词：

immune; LRRK2; gene by environment; MHCII; inflammation; HELICOBACTER-PYLORI INFECTION; ALPHA-SYNUCLEIN EXPRESSION; SODIUM-CHANNEL; ACTIVATES MICROGLIA; SUSCEPTIBILITY LOCI; CROHNS-DISEASE; KINASE LRRK2; ASSOCIATION; CYPERMETHRIN; METAANALYSIS;

D O I：

10.1002/mds.28411

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Idiopathic Parkinson's disease (iPD) is a movement disorder characterized by the degeneration of dopaminergic neurons and aggregation of the protein alpha-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. (c) 2020 International Parkinson and Movement Disorder Society

引用

页码：25 / 36

页数：12

共 125 条

[1] Association between Parkinson's disease and the HLA-DRB1 locus [J].

Ahmed, Ismail ;

Tamouza, Ryad ;

Delord, Marc ;

Krishnamoorthy, Rajagopal ;

Tzourio, Christophe ;

Mulot, Claire ;

Nacfer, Magali ;

Lambert, Jean-Charles ;

Beaune, Philippe ;

Laurent-Puig, Pierre ;

Loriot, Marie-Anne ;

Charron, Dominique ;

Elbaz, Alexis .

MOVEMENT DISORDERS, 2012, 27 (09) :1104-1110

[2] α-Synuclein-specific T cell reactivity is associated with preclinical and early Parkinson's disease [J].

Arlehamn, Cecilia S. Lindestam ;

Dhanwani, Rekha ;

Pham, John ;

Kuan, Rebecca ;

Frazier, April ;

Dutra, Juliana Rezende ;

Phillips, Elizabeth ;

Mallal, Simon ;

Roederer, Mario ;

Marder, Karen S. ;

Amara, Amy W. ;

Standaert, David G. ;

Goldman, Jennifer G. ;

Litvan, Irene ;

Peters, Bjoern ;

Sulzer, David ;

Sette, Alessandro .

NATURE COMMUNICATIONS, 2020, 11 (01)

[3] Infection with mosquito-borne alphavirus induces selective loss of dopaminergic neurons, neuroinflammation and widespread protein aggregation [J].

Bantle, Collin M. ;

Phillips, Aaron T. ;

Smeyne, Richard J. ;

Rocha, Savannah M. ;

Olson, Ken E. ;

Tjalkens, Ronald B. .

NPJ PARKINSONS DISEASE, 2019, 5 (1)

[4] Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease [J].

Barrett, Jeffrey C. ;

Hansoul, Sarah ;

Nicolae, Dan L. ;

Cho, Judy H. ;

Duerr, Richard H. ;

Rioux, John D. ;

Brant, Steven R. ;

Silverberg, Mark S. ;

Taylor, Kent D. ;

Barmada, M. Michael ;

Bitton, Alain ;

Dassopoulos, Themistocles ;

Datta, Lisa Wu ;

Green, Todd ;

Griffiths, Anne M. ;

Kistner, Emily O. ;

Murtha, Michael T. ;

Regueiro, Miguel D. ;

Rotter, Jerome I. ;

Schumm, L. Philip ;

Steinhart, A. Hillary ;

Targan, Stephan R. ;

Xavier, Ramnik J. ;

Libioulle, Cecile ;

Sandor, Cynthia ;

Lathrop, Mark ;

Belaiche, Jacques ;

Dewit, Olivier ;

Gut, Ivo ;

Heath, Simon ;

Laukens, Debby ;

Mni, Myriam ;

Rutgeerts, Paul ;

Van Gossum, Andre ;

Zelenika, Diana ;

Franchimont, Denis ;

Hugot, Jean-Pierre ;

de Vos, Martine ;

Vermeire, Severine ;

Louis, Edouard ;

Cardon, Lon R. ;

Anderson, Carl A. ;

Drummond, Hazel ;

Nimmo, Elaine ;

Ahmad, Tariq ;

Prescott, Natalie J. ;

Onnie, Clive M. ;

Fisher, Sheila A. ;

Marchini, Jonathan ;

Ghori, Jilur .

NATURE GENETICS, 2008, 40 (08) :955-962

[5] Alpha-Synuclein Expression Restricts RNA Viral Infections in the Brain [J].

Beatman, Erica L. ;

Massey, Aaron ;

Shives, Katherine D. ;

Burrack, Kristina S. ;

Chamanian, Mastooreh ;

Morrison, Thomas E. ;

Beckham, J. David .

JOURNAL OF VIROLOGY, 2016, 90 (06) :2767-2782

[6] The Function of α-Synuclein [J].

Bendor, Jacob T. ;

Logan, Todd P. ;

Edwards, Robert H. .

NEURON, 2013, 79 (06) :1044-1066

[7] LRRK2 modifies α-syn pathology and spread in mouse models and human neurons [J].

Bieri, Gregor ;

Brahic, Michel ;

Bousset, Luc ;

Couthouis, Julien ;

Kramer, Nicholas J. ;

Ma, Rosanna ;

Nakayama, Lisa ;

Monbureau, Marie ;

Defensor, Erwin ;

Schuele, Birgitt ;

Shamloo, Mehrdad ;

Melki, Ronald ;

Gitler, Aaron D. .

ACTA NEUROPATHOLOGICA, 2019, 137 (06) :961-980

[8] Significantly higher frequency of Helicobacter suis in patients with idiopathic parkinsonism than in control patients [J].

Blaecher, C. ;

Smet, A. ;

Flahou, B. ;

Pasmans, F. ;

Ducatelle, R. ;

Taylor, D. ;

Weller, C. ;

Bjarnason, I. ;

Charlett, A. ;

Lawson, A. J. ;

Dobbs, R. J. ;

Dobbs, S. M. ;

Haesebrouck, F. .

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2013, 38 (11-12) :1347-1353

[9] Expression pattern and localization of alpha-synuclein in the human enteric nervous system [J].

Boettner, Martina ;

Zorenkov, Dimitri ;

Hellwig, Ines ;

Barrenschee, Martina ;

Harde, Jonas ;

Fricke, Tobias ;

Deuschl, Guenther ;

Egberts, Jan-Hendrik ;

Becker, Thomas ;

Fritscher-Ravens, Annette ;

Arlt, Alexander ;

Wedel, Thilo .

NEUROBIOLOGY OF DISEASE, 2012, 48 (03) :474-480

[10] The biology of influenza viruses [J].

Bouvier, Nicole M. ;

Palese, Peter .

VACCINE, 2008, 26 :D49-D53

← 1 2 3 4 5 6 7 8 9 10 →