Abundance of Synaptic Vesicle-Related Proteins in Alpha-Synuclein-Containing Protein Inclusions Suggests a Targeted Formation Mechanism

Neurotoxicity Research
Amellia McCormackTim Chataway

Abstract

Proteinaceous α-synuclein-containing inclusions are found in affected brain regions in patients with Parkinson's disease (PD), Dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). These appear in neurons as Lewy bodies in both PD and DLB and as glial cytoplasmic inclusions (GCIs) in oligodendrocytes in MSA. The role they play in the pathology of the diseases is unknown, and relatively little is still known about their composition. By purifying the inclusions from the surrounding tissue and comprehensively analysing their protein composition, vital clues to the formation mechanism and role in the disease process may be found. In this study, Lewy bodies were purified from postmortem brain tissue from DLB cases (n = 2) and GCIs were purified from MSA cases (n = 5) using a recently improved purification method, and the purified inclusions were analysed by mass spectrometry. Twenty-one percent of the proteins found consistently in the GCIs and LBs were synaptic-vesicle related. Identified proteins included those associated with exosomes (CD9), clathrin-mediated endocytosis (clathrin, AP-2 complex, dynamin), retrograde transport (dynein, dynactin, spectrin) and synaptic vesicle fusion (synaptosomal-associated protein 25...Continue Reading

References

Feb 12, 1993·Brain Research·M S PollanenL Weyer
Mar 1, 1997·Movement Disorders : Official Journal of the Movement Disorder Society·G K WenningN P Quinn
Aug 15, 1998·Acta Neuropathologica·J SianM Gerlach
Sep 26, 2000·Journal of Neuroscience Research·C Richter-LandsbergV M Lee
Aug 7, 2001·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·N VanacoreUNKNOWN European Study Group on Atypical Parkinsonism (ESGAP)
Jul 9, 2003·Annals of the New York Academy of Sciences·Stanley Fahn
Dec 25, 2003·Lancet Neurology·Ian McKeithUNKNOWN International Psychogeriatric Association Expert Meeting on DLB
Jan 21, 2004·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Dennis J Cordato, Daniel K Y Chan
Dec 14, 2004·The Journal of Biological Chemistry·Evo LinderssonPoul Henning Jensen
Mar 26, 2005·Brain Research. Molecular Brain Research·Richard Jay Smeyne, Vernice Jackson-Lewis
Nov 15, 2005·Journal of Neural Transmission·N Vanacore
Nov 15, 2005·Journal of Neural Transmission·D W MillerA B Young
Sep 12, 2006·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Koichi Wakabayashi, Hitoshi Takahashi
Oct 10, 2006·Trends in Molecular Medicine·A Wood-KaczmarN W Wood
Mar 16, 2007·Journal of Neurochemistry·Jacqueline Burré, Walter Volknandt
Mar 29, 2007·Brain Pathology·James B LeverenzJing Zhang
Sep 1, 2007·Neurology·Christine Klein, Michael G Schlossmacher
Oct 18, 2007·Neurochemical Research·Isaac G Onyango
Nov 21, 2007·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Mari Yoshida
Nov 21, 2007·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Koichi WakabayashiHitoshi Takahashi
Sep 20, 2008·Journal of Neurology·Guido AlvesJan Petter Larsen
Oct 1, 2008·Annals of Neurology·Gregor K WenningMichael G Schlossmacher
Jun 23, 2009·Current Protein & Peptide Science·Vladimir N Uversky, David Eliezer
Jul 28, 2009·Journal of Proteomics·Virginie LickerPierre R Burkhard
Oct 8, 2009·Human Molecular Genetics·Hsiuchen Chen, David C Chan
Jul 11, 2014·Oxidative Medicine and Cellular Longevity·Heshan PeirisDamien J Keating
Apr 5, 2016·Journal of Neuroscience Methods·A McCormackT Chataway

❮ Previous
Next ❯

Citations

Sep 5, 2019·Acta Neuropathologica Communications·Lisa MaPaul J Hagerman
Jul 3, 2020·Frontiers in Cell and Developmental Biology·Helena S DominguesFábio G Teixeira
Dec 2, 2020·Translational Neurodegeneration·Elisabeth DinterBjörn H Falkenburger
Jan 19, 2021·The FEBS Journal·Katerina KonstantouleaJoost Schymkowitz
Jul 3, 2021·International Journal of Molecular Sciences·Alessandra MingionePaola Signorelli
Oct 13, 2021·Neurochemical Research·Abhishek Kumar Mishra, Anubhuti Dixit
Nov 30, 2021·The EMBO Journal·Katerina KonstantouleaFrederic Rousseau

❮ Previous
Next ❯

Methods Mentioned

BETA
Electrophoresis
ubiquitination
Fluorescence
density gradient centrifugation
fluorescence-activated cell sorting
electron microscopy

Software Mentioned

Adobe Photoshop
Thermo Proteome Discoverer ( PD )

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.