Neurotoxicity Research

, Volume 35, Issue 4, pp 883–897 | Cite as

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

  • Amellia McCormack
  • Damien J. Keating
  • Nusha Chegeni
  • Alex Colella
  • Jing Jing Wang
  • Tim ChatawayEmail author
Original Article


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, vesicle-associated membrane protein 2, syntaxin-1). This suggests that the misfolded or excess α-synuclein may be targeted to inclusions via vesicle-mediated transport, which also explains the presence of the neuronal protein α-synuclein within GCIs.


Lewy body Glial cytoplasmic inclusion Parkinson’s disease Multiple system atrophy Vesicle trafficking Mass spectrometry 



We would like to acknowledge Dr. Weiping Gai for the anti-α-synuclein antibody, Ms. Fariba Chegini for her assistance with immunofluoresence and the South Australian Brain Bank for their support.


This study is financially supported by the Flinders Medical Centre Research Foundation, South Australia.

Supplementary material

12640_2019_14_MOESM1_ESM.doc (1 mb)
ESM 1 (DOC 1040 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Flinders Proteomics Facility, College of Medicine and Public HealthFlinders UniversityBedford ParkAustralia
  2. 2.College of Medicine and Public HealthFlinders UniversityBedford ParkAustralia
  3. 3.Department of ImmunologyFlinders Medical Centre and Flinders University, SA PathologyBedford ParkAustralia

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