Role of complement activation and disruption of the blood–brain barrier in the pathogenesis of multiple system atrophy

•Complement plays a major role in multiple system atrophy (MSA)•Complement deposition in the cerebral vessels and myelin sheaths is evident in MSA.•Blood brain barrier disruption is potentially a key factor in MSA pathogenesis. Multiple system atrophy (MSA) is a progressive and sporadic neurodegener...

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Published in:Neuroscience letters 2024-02, Vol.822, p.137642-137642, Article 137642
Main Authors: Shibata, Makoto, Makioka, Koki, Nakamura, Takumi, Kasahara, Hiroo, Yamazaki, Tsuneo, Takatama, Masamitsu, Okamoto, Koichi, Ikeda, Yoshio
Format: Article
Language:English
Subjects:
alpha-Synuclein - metabolism
Blood-Brain Barrier - metabolism
Blood–brain barrier
Brain - metabolism
Complement
Complement activated oligodendrocytes
Complement Activation
Fibrinogen
Humans
Microglia
Microglia - metabolism
Multiple system atrophy
Multiple System Atrophy - pathology
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Summary:•Complement plays a major role in multiple system atrophy (MSA)•Complement deposition in the cerebral vessels and myelin sheaths is evident in MSA.•Blood brain barrier disruption is potentially a key factor in MSA pathogenesis. Multiple system atrophy (MSA) is a progressive and sporadic neurodegenerative disorder characterized by the histological appearance of glial cytoplasmic inclusions primarily composed of α-synuclein. Recently, complement-mediated neuroinflammation has been proposed as a key factor in the pathogenesis of numerous neurodegenerative disorders. We conducted immunohistochemical/immunofluorescent assays targeting a number of complements to explore the role of complements in MSA pathogenesis using brain samples from deceased patients and controls. Complement deposition was notably increased in the cerebral vasculature and myelin sheath in the MSA brains. Furthermore, fibrinogen leakage resulting from the disruption of the blood–brain barrier (BBB) was observed, along with the presence of C1q-positive microglia clusters surrounding the MSA brain vessels. These immunohistochemical/immunofluorescent findings suggest that complement activation and BBB disruption play critical roles in MSA progression.
ISSN:0304-3940
1872-7972
DOI:10.1016/j.neulet.2024.137642