Axonal transport and secretion of fibrillar forms of α-synuclein, Aβ42 peptide and HTTExon 1

Acta Neuropathologica
Michel BrahicAaron D Gitler

Abstract

Accruing evidence suggests that prion-like behavior of fibrillar forms of α-synuclein, β-amyloid peptide and mutant huntingtin are responsible for the spread of the lesions that characterize Parkinson disease, Alzheimer disease and Huntington disease, respectively. It is unknown whether these distinct protein assemblies are transported within and between neurons by similar or distinct mechanisms. It is also unclear if neuronal death or injury is required for neuron-to-neuron transfer. To address these questions, we used mouse primary cortical neurons grown in microfluidic devices to measure the amounts of α-synuclein, Aβ42 and HTTExon1 fibrils transported by axons in both directions (anterograde and retrograde), as well as to examine the mechanism of their release from axons after anterograde transport. We observed that the three fibrils were transported in both anterograde and retrograde directions but with strikingly different efficiencies. The amount of Aβ42 fibrils transported was ten times higher than that of the other two fibrils. HTTExon1 was efficiently transported in the retrograde direction but only marginally in the anterograde direction. Finally, using neurons from two distinct mutant mouse strains whose axons are h...Continue Reading

References

Mar 8, 1984·The New England Journal of Medicine·S B Prusiner
Oct 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·M F LyonV H Perry
May 1, 1999·The Journal of Biological Chemistry·C ThualR Melki
Nov 5, 2002·The American Journal of Pathology·Reisuke H TakahashiGunnar K Gouras
Jul 19, 2005·Neurobiology of Aging·Gunnar K GourasReisuke H Takahashi
Aug 12, 2005·Nature Methods·Anne M TaylorNoo Li Jeon
Feb 10, 2006·The EMBO Journal·Joanna Krzewska, Ronald Melki
Mar 23, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Subhojit RoyVirginia M-Y Lee
Dec 20, 2007·Science's STKE : Signal Transduction Knowledge Environment·Marc Dalod
Mar 27, 2009·Proceedings of the National Academy of Sciences of the United States of America·G PiginoS Brady
Jun 9, 2009·Nature Cell Biology·Florence ClavagueraMarkus Tolnay
Aug 19, 2009·Journal of Neurochemistry·Karin M DanzerBastian Hengerer
Sep 30, 2009·Experimental Neurology·Jeffrey H Kordower, Patrik Brundin
Nov 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Kelvin C LukVirginia M-Y Lee
Apr 2, 2010·Journal of Cell Science·Mimi CushmanJames Shorter
May 21, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Evangelia EmmanouilidouKostas Vekrellis
Jul 9, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Helena DeckerMichael A Silverman
Sep 2, 2010·The Journal of Biological Chemistry·Takashi NonakaMasato Hasegawa
Jan 20, 2011·The Journal of Clinical Investigation·Christian HansenPatrik Brundin
Feb 10, 2011·Neurobiology of Disease·Lydia Alvarez-ErvitiJ Mark Cooper
Jan 11, 2012·The Journal of Cell Biology·Jack T WangBen A Barres
Mar 1, 2012·Neuron·Alix de CalignonBradley T Hyman
Mar 31, 2012·The Journal of Biological Chemistry·Najla KfouryMarc I Diamond
Jun 9, 2012·Science·Jeannette M OsterlohMarc R Freeman
Jun 28, 2012·Biophysical Journal·Laura PieriRonald Melki
Oct 31, 2012·Annals of Neurology·Eric C FreundtMichel Brahic
Aug 6, 2013·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Subhojit Roy
Sep 17, 2013·Cell·Adriano Aguzzi, Aaron D Gitler
Oct 11, 2013·Nature Communications·Luc BoussetRonald Melki
May 7, 2014·Annals of Neurology·Francesca CicchettiThomas B Freeman
Jul 16, 2014·Nature Neuroscience·Eline Pecho-VrieselingFrancesco Paolo Di Giorgio
Nov 14, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Taiji TsunemiDimitri Krainc

❮ Previous
Next ❯

Citations

Apr 15, 2016·Scientific Reports·Laura PieriRonald Melki
Feb 24, 2017·Molecular Neurobiology·Laura UrreaJosé Antonio Del Río
Mar 12, 2017·Journal of Parkinson's Disease·Heiko Braak, Kelly Del Tredici
Feb 9, 2018·Journal of Neural Transmission·S BräuerA Hermann
Dec 1, 2017·NPJ Parkinson's Disease·Bryan Andrew Killinger, Viviane Labrie
May 16, 2018·Cellular and Molecular Life Sciences : CMLS·Didier VilettePascal Leblanc
Feb 15, 2019·Laboratory Investigation; a Journal of Technical Methods and Pathology·Richard J KarpowiczVirginia M-Y Lee
Jul 10, 2019·Journal of Neurochemistry·D J VidyadharaSreeganga S Chandra
Jun 4, 2016·Current Opinion in Neurology·Patrik BrundinJeffrey H Kordower
Jun 4, 2019·Journal of Neurochemistry·Bryan A Killinger, Jeffrey H Kordower
Mar 24, 2020·Nature Reviews. Neurology·Chao PengVirginia M-Y Lee
Mar 7, 2020·Biomolecules·Margaux TeilBenjamin Dehay
May 12, 2020·Wiley Interdisciplinary Reviews. Developmental Biology·Amrita PathakBruce D Carter
Aug 10, 2016·Journal of Neurochemistry·Eva-Maria Hock, Magdalini Polymenidou
Jul 7, 2016·The Journal of Biological Chemistry·Airi TarutaniMasato Hasegawa
Jun 8, 2018·Frontiers in Neuroscience·Lilia RodriguezAnurag Tandon
Jan 11, 2020·Frontiers in Neurology·Jamie C BlairT Jason Druzgal
Jun 3, 2020·Nature Communications·Christoph GerdesFelipe Opazo
Oct 6, 2020·Frontiers in Bioengineering and Biotechnology·Jose A Del Rio, Isidre Ferrer
Jul 6, 2019·Frontiers in Neuroscience·Jiangnan MaAnmu Xie
Apr 21, 2020·Oxidative Medicine and Cellular Longevity·Annika HöhnRoberta Cascella
Sep 28, 2018·Nature Neuroscience·Mathias Jucker, Lary C Walker
Oct 22, 2019·Frontiers in Molecular Neuroscience·Marina Friesen, Melanie Meyer-Luehmann
Jul 21, 2017·The Journal of Cell Biology·Guiliana Soraya Victoria, Chiara Zurzolo
Dec 13, 2018·Neurology and Therapy·Samis M A ZellaLars Tönges
Mar 31, 2019·Acta Neuropathologica·Gregor BieriAaron D Gitler
Jan 31, 2020·Neuroscience and Biobehavioral Reviews·Brendan B McAllisterMajid H Mohajerani
Oct 27, 2020·Journal of Parkinson's Disease·Anne-Marie CastonguayMartin Lévesque
Feb 15, 2021·Journal of Neuroscience Research·Paul M HollowayMichele Zagnoni
Mar 13, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Xiao-Tong WangYu-He Yuan
Dec 15, 2019·Neurobiology of Disease·Lindsay E StoykaLaura A Volpicelli-Daley
Mar 24, 2021·Nature Communications·Roberta CascellaCristina Cecchi

❮ Previous
Next ❯

Methods Mentioned

BETA
transmission electron microscopy
fluorescence spectroscopy

Software Mentioned

Data Explorer

Related Concepts

Related Feeds

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Alpha-Synuclein Aggregation

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.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.

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.