Extracellular α-synuclein levels are regulated by neuronal activity

Molecular Neurodegeneration
Kaoru Yamada, Takeshi Iwatsubo

Abstract

α-Synuclein is a presynaptic protein abundant in the cytoplasmic compartment of neurons, whereas its presence in the extracellular space has also been observed under physiological conditions. Extracellular α-synuclein has pathological significance, exhibiting cellular toxicity and impairment of synaptic transmission. Notably, misfolded α-synuclein drives the cell-to-cell propagation of pathology via the extracellular space. However, the primary mechanism that regulates the extracellular levels of α-synuclein remains to be determined. Using several mechanistically distinct methods to modulate neuronal/synaptic activities in primary neuronal culture and in vivo microdialysis, we examined the involvement of neuronal/synaptic activities on α-synuclein release. We demonstrate here that physiological release of endogenous α-synuclein highly depends on intrinsic neuronal activities. Elevating neuronal activity rapidly increased, while blocking activity decreased, α-synuclein release. In vivo microdialysis experiments in freely moving mice revealed that ~ 70% of extracellular α-synuclein arises from neuronal activity-dependent pathway. Selective modulation of glutamatergic neurotransmission altered extracellular α-synuclein levels, imp...Continue Reading

References

Aug 28, 1997·Nature·M G SpillantiniM Goedert
Aug 25, 2001·Annual Review of Neuroscience·T C Südhof
Jun 25, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·He-Jin LeeSeung-Jae Lee
Dec 21, 2005·Neuron·John R CirritoDavid M Holtzman
Apr 21, 2010·Neuroscience Research·Harutsugu TatebeTakahiko Tokuda
May 21, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Evangelia EmmanouilidouKostas Vekrellis
Sep 30, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Karin M DanzerPamela J McLean
Jul 23, 2011·PloS One·Evangelia EmmanouilidouKostas Vekrellis
Sep 16, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Kaoru YamadaDavid M Holtzman
Jan 25, 2012·Neuro-degenerative Diseases·Diana SimónJesús Avila
Feb 9, 2012·Proceedings of the National Academy of Sciences of the United States of America·Martin LundbladAnders Björklund
Aug 24, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Maria José DiógenesTiago Fleming Outeiro
Aug 28, 2012·Molecular Neurodegeneration·Karin M DanzerPamela J McLean
Jan 3, 2013·Journal of Neurochemistry·Sébastien PaillussonPascal Derkinderen
Feb 16, 2013·EMBO Reports·Amy M PoolerDiane P Hanger
Jul 31, 2013·Neurobiology of Aging·Katerina MelachroinouKostas Vekrellis
Jan 29, 2014·Nature Reviews. Neurology·He-Jin LeeSeung-Jae Lee
Feb 19, 2014·The Journal of Experimental Medicine·Kaoru YamadaDavid M Holtzman
Mar 4, 2014·PloS One·Katsutoshi TaguchiMasaki Tanaka
Aug 8, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Giuseppe RonzittiEvelina Chieregatti
Sep 2, 2015·The EMBO Journal·Amulya Nidhi ShrivastavaAntoine Triller
Oct 28, 2015·Molecular Neurodegeneration·Kaoru YamadaDavid M Holtzman
Feb 26, 2016·Brain : a Journal of Neurology·Evangelia EmmanouilidouKostas Vekrellis
Jun 21, 2016·Nature Neuroscience·Jessica W WuKaren E Duff
Jun 21, 2016·EBioMedicine·Marco EmanueleEvelina Chieregatti

❮ Previous
Next ❯

Citations

Jan 27, 2019·The Journal of Comparative Neurology·Deanna L Benson, George W Huntley
Jul 31, 2019·Movement Disorders : Official Journal of the Movement Disorder Society·Brit MollenhauerUNKNOWN PPMI study
Nov 5, 2019·Movement Disorders : Official Journal of the Movement Disorder Society·Md Ezazul HaqueDong-Kug Choi
Feb 15, 2020·Annals of Neurology·Nicolas R BarthélemyBrendan P Lucey
Mar 24, 2020·Nature Reviews. Neurology·Chao PengVirginia M-Y Lee
Jul 11, 2018·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Ana I Rodriguez-PerezJose L Labandeira-Garcia
Apr 22, 2019·Acta Neuropathologica·Javier Alegre-AbarrateguiChristos Proukakis
Nov 14, 2019·Scientific Reports·Anett HudákTamás Letoha
Jul 28, 2020·International Journal of Molecular Sciences·Ching-On Wong
Sep 26, 2020·Frontiers in Molecular Neuroscience·Naila Kuhlmann, Austen J Milnerwood
Aug 22, 2018·Frontiers in Cellular Neuroscience·Sara A Ferreira, Marina Romero-Ramos
Sep 28, 2018·Nature Neuroscience·Mathias Jucker, Lary C Walker
Oct 28, 2019·Frontiers in Molecular Neuroscience·Emmanouela LeandrouKostas Vekrellis
Dec 4, 2019·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Eiko N Minakawa
May 12, 2020·Frontiers in Pharmacology·Mónica Gómez-BenitoRosario Moratalla
Mar 20, 2019·Annals of Neurology·Simon J SchreinerChristian R Baumann
Sep 12, 2020·Cells·Enrico Zampese, D James Surmeier
Aug 23, 2020·Biomolecules·Carl Alexander SandhofCarmen Nussbaum-Krammer
Dec 24, 2018·International Journal of Molecular Sciences·Dario ValdinocciDean L Pountney
May 21, 2019·Frontiers in Molecular Neuroscience·Eftychia VasiliTiago Fleming Outeiro
Feb 7, 2020·Science Translational Medicine·Albert A DavisDavid M Holtzman
Dec 2, 2020·Translational Neurodegeneration·Elisabeth DinterBjörn H Falkenburger
Jan 19, 2021·Journal of Molecular Neuroscience : MN·Lina PanZhentao Zhang
Nov 13, 2020·Science Advances·Martin T HenrichD James Surmeier
May 7, 2020·Trends in Molecular Medicine·Norihito UemuraJohn Q Trojanowski
Apr 5, 2021·Movement Disorders : Official Journal of the Movement Disorder Society·Jun UedaRyosuke Takahashi
Jan 29, 2019·Ageing Research Reviews·Jessica Y VargasChiara Zurzolo
Jun 3, 2021·International Journal of Molecular Sciences·Panagiota Mavroeidi, Maria Xilouri
Jul 25, 2021·Movement Disorders : Official Journal of the Movement Disorder Society·Dalton James Surmeier
Sep 11, 2021·Molecular Neurodegeneration·Grace M LloydDavid R Borchelt
May 28, 2021·CNS & Neurological Disorders Drug Targets·Jet Shee TengRhun Yian Koh
Sep 26, 2021·Molecular Psychiatry·Yu-Jie GuoPeng Lei

❮ Previous
Next ❯

Methods Mentioned

BETA
size exclusion chromatography
ELISA
size-exclusion chromatography

Software Mentioned

Prism
Graph Pad

Related Concepts

Related Feeds

Alpha-Synuclein Aggregation (MDS)

Alpha-synucleins are small proteins that are believed to restrict the mobility of synpatic vesicles and inhibit neurotransmitter release. Aggregation of these proteins have been linked to several types of neurodegenerative diseases including dementia with Lewy bodies and Parkinson's disease. Here is the latest research on α-synuclein aggregation.