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Immunotherapy Targeting Neurodegenerative Proteinopathies: α-Synucleinopathies and Tauopathies
Junghwan Shin, Han-Joon Kim, Beomseok Jeon
J Mov Disord. 2020;13(1):11-19.   Published online December 19, 2019
DOI: https://doi.org/10.14802/jmd.19057
  • 10,288 View
  • 457 Download
  • 19 Web of Science
  • 19 Crossref
AbstractAbstract PDF
α-Synuclein and tau deposition in the central nervous system is responsible for various parkinsonian syndromes, including Parkinson’s disease, multiple system atrophy, dementia with Lewy bodies, progressive supranuclear palsy and corticobasal degeneration. Emerging evidence has suggested that pathologic α-synuclein and tau are transmitted from cell to cell and further accelerate the aggregation of pathologic proteins in neighboring cells. Furthermore, extracellular pathologic proteins have also been reported to provoke inflammatory responses that lead to neurodegeneration. Therefore, immunotherapies targeting extracellular α-synuclein and tau have been proposed as potential disease-modifying strategies. In this review, we summarize completed phase I trials and ongoing phase II trials of immunotherapies against α-synuclein and tau and further discuss concerns and hurdles to overcome in the future.

Citations

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    International Journal of Molecular Sciences.2020; 21(15): 5295.     CrossRef
  • Novel antibodies detect additional α-synuclein pathology in synucleinopathies: potential development for immunotherapy
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    Alzheimer's Research & Therapy.2020;[Epub]     CrossRef
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    Frontiers in Molecular Neuroscience.2020;[Epub]     CrossRef
Mechanism of Anti-α-Synuclein Immunotherapy
Jun Sung Lee, Seung-Jae Lee
J Mov Disord. 2016;9(1):14-19.   Published online January 25, 2016
DOI: https://doi.org/10.14802/jmd.15059
  • 25,517 View
  • 332 Download
  • 35 Web of Science
  • 35 Crossref
AbstractAbstract PDF
Immunization therapy targeting α-synuclein has emerged as a promising approach for Parkinson’s disease and perhaps for other synucleinopathies. Several antibodies have shown therapeutic effects in mouse models of synucleinopathies and have alleviated the pathological and behavioral phenotypes of these mice. The mechanisms through which the immunization therapy works were initially puzzling, especially given that α-synuclein is a typical cytosolic protein. Recent studies, however, suggested that extracellular α-synuclein is an important pathogenic entity, and hence, a target for immunotherapy. Here, we review the literature describing immunization therapy for synucleinopathies in mouse models and provide current thoughts on the potential mechanisms underlying the therapeutic effects of α-synuclein immunotherapy.

Citations

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JMD : Journal of Movement Disorders