A functional role for alpha-synuclein in neuroimmune responses

Alpha-synuclein is a neuronal protein with unclear function but is associated with the pathogenesis of Parkinson's disease and other synucleinopathies. In this review, we discuss the emerging functional role of alpha-synuclein in support of the unique immune responses in the nervous system. Rec...

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Published in:	Journal of neuroimmunology Vol. 376; p. 578047
Main Authors:	Heiden, Dustin L., Monogue, Brendan, Ali, M.D. Haider, Beckham, J. David
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier B.V 15-03-2023
Subjects:	Alpha-synuclein Humans Immunity Neurodegeneration Neuroimmunology Neuroinflammation Neurons - metabolism Parkinson Disease - metabolism Parkinson's disease Parkinson's disease Neuroinflammation CNS Immunity IFN PD PNS Neurodegeneration α-syn MSA DLB Neuroimmunology ISG Alpha-synuclein
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Abstract	Alpha-synuclein is a neuronal protein with unclear function but is associated with the pathogenesis of Parkinson's disease and other synucleinopathies. In this review, we discuss the emerging functional role of alpha-synuclein in support of the unique immune responses in the nervous system. Recent data now show that alpha-synuclein functions to support interferon signaling within neurons and is released from neurons to support chemoattraction and activation of local glial cells and infiltrating immune cells. Inflammatory activation and interferon signaling also induce post-translational modifications of alpha-synuclein that are commonly associated with Parkinson's disease pathogenesis. Taken together, emerging data implicate complex interactions between alpha-synuclein and host immune responses that may contribute to the pathogenesis of Parkinson's disease. Additional study of the function of alpha-synuclein in the brain's immune response may provide disease-modifying therapeutic targets for Parkinson's disease in the future. •Alpha-synuclein is associated with the pathogenesis of Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy.•Recent work has shown that alpha-synuclein functions to support neuronal and microglia innate immune responses.•Alpha-synuclein interacts with the type 1 interferon signaling pathway in neurons to support interferon stimulated gene expression.•Alpha-synuclein is released from neurons resulting in activation of microglia, astrocytes, and infiltrating innate and adaptive immune cells.
AbstractList	Alpha-synuclein is a neuronal protein with unclear function but is associated with the pathogenesis of Parkinson's disease and other synucleinopathies. In this review, we discuss the emerging functional role of alpha-synuclein in support of the unique immune responses in the nervous system. Recent data now show that alpha-synuclein functions to support interferon signaling within neurons and is released from neurons to support chemoattraction and activation of local glial cells and infiltrating immune cells. Inflammatory activation and interferon signaling also induce post-translational modifications of alpha-synuclein that are commonly associated with Parkinson's disease pathogenesis. Taken together, emerging data implicate complex interactions between alpha-synuclein and host immune responses that may contribute to the pathogenesis of Parkinson's disease. Additional study of the function of alpha-synuclein in the brain's immune response may provide disease-modifying therapeutic targets for Parkinson's disease in the future. •Alpha-synuclein is associated with the pathogenesis of Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy.•Recent work has shown that alpha-synuclein functions to support neuronal and microglia innate immune responses.•Alpha-synuclein interacts with the type 1 interferon signaling pathway in neurons to support interferon stimulated gene expression.•Alpha-synuclein is released from neurons resulting in activation of microglia, astrocytes, and infiltrating innate and adaptive immune cells. Alpha-synuclein is a neuronal protein with unclear function but is associated with the pathogenesis of Parkinson's disease and other synucleinopathies. In this review, we discuss the emerging functional role of alpha-synuclein in support of the unique immune responses in the nervous system. Recent data now show that alpha-synuclein functions to support interferon signaling within neurons and is released from neurons to support chemoattraction and activation of local glial cells and infiltrating immune cells. Inflammatory activation and interferon signaling also induce post-translational modifications of alpha-synuclein that are commonly associated with Parkinson's disease pathogenesis. Taken together, emerging data implicate complex interactions between alpha-synuclein and host immune responses that may contribute to the pathogenesis of Parkinson's disease. Additional study of the function of alpha-synuclein in the brain's immune response may provide disease-modifying therapeutic targets for Parkinson's disease in the future.
ArticleNumber	578047
Author	Heiden, Dustin L. Ali, M.D. Haider Beckham, J. David Monogue, Brendan
AuthorAffiliation	a Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA c Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA d Rocky Mountain Regional VA Medical Center, Aurora, CO, USA b Department of Medicine, Division of Infectious Diseases, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
AuthorAffiliation_xml	– name: b Department of Medicine, Division of Infectious Diseases, University of Colorado Anschutz Medical Campus, Aurora, CO, USA – name: a Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA – name: c Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA – name: d Rocky Mountain Regional VA Medical Center, Aurora, CO, USA
Author_xml	– sequence: 1 givenname: Dustin L. surname: Heiden fullname: Heiden, Dustin L. organization: Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA – sequence: 2 givenname: Brendan surname: Monogue fullname: Monogue, Brendan organization: Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA – sequence: 3 givenname: M.D. Haider surname: Ali fullname: Ali, M.D. Haider organization: Department of Medicine, Division of Infectious Diseases, University of Colorado Anschutz Medical Campus, Aurora, CO, USA – sequence: 4 givenname: J. David surname: Beckham fullname: Beckham, J. David email: David.beckham@cuanschutz.edu organization: Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/36791583$$D View this record in MEDLINE/PubMed
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Keywords	Parkinson's disease Neuroinflammation CNS Immunity IFN PD PNS Neurodegeneration α-syn MSA DLB Neuroimmunology ISG Alpha-synuclein
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Snippet	Alpha-synuclein is a neuronal protein with unclear function but is associated with the pathogenesis of Parkinson's disease and other synucleinopathies. In this... Alpha-synuclein is a neuronal protein with unclear function but is associated with the pathogenesis of Parkinson’s disease and other synucleinopathies. In this...
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SubjectTerms	Alpha-synuclein Humans Immunity Neurodegeneration Neuroimmunology Neuroinflammation Neurons - metabolism Parkinson Disease - metabolism Parkinson's disease
Title	A functional role for alpha-synuclein in neuroimmune responses
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