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Acta Neuropathol Commun. 2018 Feb 8;6(1):8. doi: 10.1186/s40478-018-0509-1.

Lack of pathogenic potential of peripheral α-synuclein aggregates from Parkinson's disease patients.

Author information

1
Neurodegenerative Diseases Research Group, Vall d'Hebron Research Institute-Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), 08035, Barcelona, Spain.
2
Neurological Tissue Bank, Biobanc Hospital Clínic-IDIBAPS, 08036, Barcelona, Spain.
3
Institute of Neurology, Medical University of Vienna, 1090, Vienna, Austria.
4
Parkinson's Disease and Movement Disorders Unit, Institut Clínic de Neurociències, Hospital Clinic of Barcelona-CIBERNED, 08036, Barcelona, Spain.
5
Neurodegenerative Diseases Research Group, Vall d'Hebron Research Institute-Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), 08035, Barcelona, Spain. miquel.vila@vhir.org.
6
Department of Biochemistry and Molecular Biology, Autonomous University of Barcelona, 08193, Barcelona, Spain. miquel.vila@vhir.org.
7
Catalan Institution for Research and Advanced Studies (ICREA), 08010, Barcelona, Spain. miquel.vila@vhir.org.

Abstract

In Parkinson's disease (PD) there is widespread accumulation in the brain of abnormal α-synuclein aggregates forming intraneuronal Lewy bodies (LB). It is now well established that LB-type α-synuclein aggregates also occur in the peripheral autonomic nervous system in PD, from where it has been speculated they may progressively spread to the central nervous system through synaptically-connected brain networks and reach the substantia nigra to trigger herein dopaminergic dysfunction/degeneration and subsequent parkinsonism. Supporting a pathogenic role for α-synuclein aggregates we have previously shown that LB purified from postmortem PD brains promote α-synuclein pathology and dopaminergic neurodegeneration when intracerebrally inoculated into wild-type mice. However, the pathogenic capacity of PD-derived peripheral α-synuclein aggregates remains unknown. Here we addressed this question using purified LB-type α-synuclein aggregates from postmortem PD stellate ganglia (SG), a paravertebral sympathetic ganglion that exhibits consistent and conspicuous Lewy pathology in all PD patients. In contrast to our previous findings using nigral LB extracts, intracerebral inoculation of SG-derived LB into mice did not trigger long-term nigrostriatal neurodegeneration nor α-synuclein pathology. The differential pathogenic capacities of central- and peripheral-derived α-synuclein aggregates appear independent of the absolute amount and basic biochemical properties of α-synuclein within these aggregates and may rely instead on differences in α-synuclein conformation and/or yet unrecognized brain region-specific intrinsic factors. Our results argue against a putative pathogenic capacity of peripheral α-synuclein aggregates to promote α-synuclein pathology in the brain, propagate between neuronal networks or induce neurodegeneration.

PMID:
29422109
PMCID:
PMC5806361
DOI:
10.1186/s40478-018-0509-1
[Indexed for MEDLINE]
Free PMC Article

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