Region-Specific Effects of Immunotherapy With Antibodies Targeting α-synuclein in a Transgenic Model of Synucleinopathy

Frontiers in Neuroscience
Martin KallabNadia Stefanova

Abstract

Synucleinopathies represent a group of neurodegenerative disorders which are characterized by intracellular accumulation of aggregated α-synuclein. α-synuclein misfolding and oligomer formation is considered a major pathogenic trigger in these disorders. Therefore, targeting α-synuclein species represents an important candidate therapeutic approach. Our aim was to analyze the biological effects of passive immunization targeting α-synuclein and to identify the possible underlying mechanisms in a transgenic mouse model of oligodendroglial α-synucleinopathy. We used PLP-α-synuclein mice overexpressing human α-synuclein in oligodendrocytes. The animals received either antibodies that recognize α-synuclein or vehicle. Passive immunization mitigated α-synuclein pathology and resulted in reduction of total α-synuclein in the hippocampus, reduction of intracellular accumulation of aggregated α-synuclein, particularly significant in the spinal cord. Lowering of the extracellular oligomeric α-synuclein was associated with reduction of the density of activated iba1-positive microglia profiles. However, a shift toward phagocytic microglia was seen after passive immunization of PLP-α-synuclein mice. Lowering of intracellular α-synuclein was...Continue Reading

References

Mar 26, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Wei ZhangJing Zhang
Oct 13, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Susan A AustinColin K Combs
Sep 14, 2007·Movement Disorders : Official Journal of the Movement Disorder Society·Nadia StefanovaGregor K Wenning
May 13, 2011·Acta Neuropathologica·Lisa FellnerNadia Stefanova
Jun 16, 2011·Annals of Neurology·Viktor BartanuszMurat Digicaylioglu
Aug 2, 2011·The American Journal of Pathology·Nadia StefanovaGregor K Wenning
Aug 2, 2012·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Ethan A WinklerBerislav V Zlokovic
Sep 4, 2012·Molecular Neurobiology·Lisa Fellner, Nadia Stefanova
Sep 28, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Eun-Jin BaeSeung-Jae Lee
May 24, 2014·Neurobiology of Disease·Veronica LindströmMartin Ingelsson
Jul 11, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Dora GamesEliezer Masliah
Jan 15, 2015·Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society·Nadia Stefanova, Gregor K Wenning
Apr 16, 2015·Biomolecules·Tomás Lopes da FonsecaTiago Fleming Outeiro
Oct 16, 2015·Journal of Neurochemistry·Tomasz BrudekBente Pakkenberg
Feb 2, 2016·Journal of Movement Disorders·Jun Sung Lee, Seung-Jae Lee
May 4, 2016·Tissue Barriers·Imola WilhelmIstván A Krizbai
Aug 3, 2016·Proceedings of the National Academy of Sciences of the United States of America·Fares BassilWassilios G Meissner
Feb 9, 2017·Nature Medicine·Yvette C Wong, Dimitri Krainc
Mar 24, 2017·Brain : a Journal of Neurology·Fares BassilWassilios G Meissner
Jul 28, 2017·Nature Reviews. Neuroscience·James B KoprichJonathan M Brotchie
Sep 2, 2017·Journal of Neurology, Neurosurgery, and Psychiatry·Shunsuke Koga, Dennis W Dickson
Oct 11, 2017·Experimental Neurology·Patrik BrundinJeffrey H Kordower
Oct 12, 2017·Autonomic Neuroscience : Basic & Clinical·Nadia Stefanova
Dec 17, 2017·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Edward RockensteinRobert A Rissman
Feb 27, 2018·Cell and Tissue Research·Jennifer A SteinerPatrik Brundin

❮ Previous
Next ❯

Citations

Aug 9, 2020·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Matthew R Burns, Nikolaus R McFarland
Oct 6, 2020·Frontiers in Cell and Developmental Biology·Maria FoukaMaria Xilouri
Mar 13, 2020·Frontiers in Immunology·Oluwaseun FatobaToshihide Yamashita
Nov 21, 2020·International Journal of Molecular Sciences·Xiao-Yu DuRui-Tian Liu
Aug 17, 2021·Journal of Neural Transmission·Miguel LemosNadia Stefanova

❮ Previous
Next ❯

Methods Mentioned

BETA
transgenic
ELISA
electrophoresis
Confocal microscopy

Software Mentioned

GraphPad Prism
MicroBrightField
Huygens Professional
StereoInvestigator
Leica LAS X
FusionCapt Advance

Related Concepts

Related Feeds

Basal Ganglia

Basal Ganglia are a group of subcortical nuclei in the brain associated with control of voluntary motor movements, procedural and habit learning, emotion, and cognition. Here is the latest research.

Autophagy & Disease

Autophagy is an important cellular process for normal physiology and both elevated and decreased levels of autophagy are associated with disease. Here is the latest research.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms