@inbook{c4cd0aeb385846708103a32de31c9f25,
title = "Can infections trigger alpha-synucleinopathies?",
abstract = "As synucleinopathies, Parkinson's disease (PD) and multiple system atrophy (MSA) are neurodegenerative diseases that involve the spread of pathogenic alpha-synuclein (αSyn) throughout the brain. Recent studies have suggested a role for αSyn as an antimicrobial peptide in response to PD- and MSA-related infections of peripheral tissues, including those in the respiratory, gastrointestinal, and urogenital systems. In this chapter, we examine epidemiological and experimental evidence for a role of peripheral microbial infections in triggering alpha-synucleinopathies. We propose a model of how infectious triggers, in conjunction with inflammatory, environmental, and genetic facilitators, may result in transfer of pathogenic αSyn strains from the periphery to the brain, where they propagate and spread. Finally, we discuss future research challenges and programs necessary to clarify the role of infections as triggers of PD and MSA and, ultimately, to prevent the onset of these diseases by infectious triggers.",
keywords = "Alpha-synuclein, Antimicrobial peptides, Bacteria, Facilitators, Fungi, Infections, Multiple system atrophy, Parkinson's disease, Triggers, Viruses",
author = "Tulisiak, {Christopher T.} and Gabriela Mercado and Wouter Peelaerts and Lena Brundin and Patrik Brundin",
note = "Funding Information: We acknowledge the Van Andel Research Institute and the many individuals and corporations that supported financially the neurodegenerative research at Van Andel Research Institute. We would like to acknowledge Farmer Family Foundation for funding related to the topic of this review. P.B. is supported by grants from the National Institutes of Health (1R01DC016519-03) which supports G.M. and the Office of the Assistant Secretary of Defense for Health Affairs (Parkinson's Research Program, Award No. W81XWH-17-1-0534) which supports C.T. L.B. is supported by grant 14939 from the Michael J. Fox Foundation. W.P. is supported by a Fulbright Fellowship and FWO. P.B. has received commercial support as a consultant from Renovo Neural, Inc. Roche, Teva Inc. Lundbeck A/S, AbbVie, Neuroderm, Fujifilm-Cellular Dynamics International, Axial Biotherapeutics, ClearView Healthcare, FCB Health, IOS Press Partners and Capital Technologies, Inc. He has received commercial support for grants/research from Renovo and Roche. He has ownership interests in Acousort AB and is on the steering committee of the NILO-PD trial. The authors declare no additional competing financial interests. Funding Information: We acknowledge the Van Andel Research Institute and the many individuals and corporations that supported financially the neurodegenerative research at Van Andel Research Institute. We would like to acknowledge Farmer Family Foundation for funding related to the topic of this review. P.B. is supported by grants from the National Institutes of Health (1R01DC016519-03) which supports G.M. and the Office of the Assistant Secretary of Defense for Health Affairs (Parkinson's Research Program, Award No. W81XWH-17-1-0534) which supports C.T. L.B. is supported by grant 14939 from the Michael J. Fox Foundation. W.P. is supported by a Fulbright Fellowship and FWO. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",
year = "2019",
doi = "10.1016/bs.pmbts.2019.06.002",
language = "English (US)",
isbn = "9780128178744",
series = "Progress in Molecular Biology and Translational Science",
publisher = "Elsevier B.V.",
pages = "299--322",
editor = "Teplow, {David B.}",
booktitle = "Molecular Biology of Neurodegenerative Diseases",
}