Stochastic Optical Reconstruction Microscopy Imaging of Multiple System Atrophy Inclusions Suggests Stepwise α-Synuclein Aggregation.
Mov Disord
; 39(4): 723-728, 2024 Apr.
Article
in En
| MEDLINE
| ID: mdl-38357858
ABSTRACT
BACKGROUND:
The architecture and composition of glial (GCI) and neuronal (NCI) α-synuclein inclusions observed in multiple system atrophy (MSA) remain to be precisely defined to better understand the disease.METHODS:
Here, we used stochastic optical reconstruction microscopy (STORM) to characterize the nanoscale organization of glial (GCI) and neuronal (NCI) α-synuclein inclusions in cryopreserved brain sections from MSA patients.RESULTS:
STORM revealed a dense cross-linked internal structure of α-synuclein in all GCI and NCI. The internal architecture of hyperphosphorylated α-synuclein (p-αSyn) inclusions was similar in glial and neuronal cells, suggesting a common aggregation mechanism. A similar sequence of p-αSyn stepwise intracellular aggregation was defined in oligodendrocytes and neurons, starting from the perinuclear area and growing inside the cells. Consistent with this hypothesis, we found a higher mitochondrial density in GCI and NCI compared to oligodendrocytes and neurons from unaffected donors (P < 0.01), suggesting an active recruitment of the organelles during the aggregation process.CONCLUSIONS:
These first STORM images of GCI and NCI suggest stepwise α-synuclein aggregation in MSA. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Inclusion Bodies
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Multiple System Atrophy
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Alpha-Synuclein
/
Neurons
Limits:
Aged
/
Female
/
Humans
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Male
/
Middle aged
Language:
En
Journal:
Mov Disord
Journal subject:
NEUROLOGIA
Year:
2024
Document type:
Article
Affiliation country:
Francia
Country of publication:
Estados Unidos