Histones facilitate α-synuclein aggregation during neuronal apoptosis
Peizhou Jiang1, Ming Gan2,3, Shu-Hui Yen2
1Department of Neuroscience, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL, 32224, USA. Jiang.peizhou@mayo.edu.
Acta Neuropathologica
|December 23, 2016
Summary
Histones, found in the cell nucleus, promote the formation of toxic alpha-synuclein (αS) aggregates in Parkinson's disease (PD). These histone-induced αS aggregates are transmissible, offering new insights into PD
Area of Science:
- Neuroscience
- Cell Biology
- Pathology
Background:
- Intercellular transmission of alpha-synuclein (αS) contributes to Parkinson's disease (PD) pathology spread.
- The origin of initial, transmissible αS aggregates remains unclear.
- Previous work linked neuronal nuclear membrane defects to αS aggregation and seeding.
Purpose of the Study:
- Identify nuclear factors promoting αS aggregation.
- Investigate the role of these factors in apoptotic neurons and PD brains.
- Determine the characteristics and transmissibility of histone-induced αS aggregates.
Main Methods:
- In vitro and in vivo experiments.
- Analysis of αS aggregation in apoptotic neurons and PD brain tissue.
- Characterization of αS aggregate species (oligomers, protofibrils, fibrils).
- Stereotactic injection in mouse brains to assess transmissibility.
Main Results:
- Histones identified as nuclear proaggregant factors for αS.
- Histone-induced αS aggregates comprise diverse oligomeric forms.
- These aggregates exhibit seeding potential and are transmissible in vivo.
- Demonstrated transmissibility of αS aggregates in mouse brains via stereotactic injection.
Conclusions:
- Histones are implicated in the initial formation of pathological αS aggregates.
- Histone-induced αS aggregates contribute to PD pathogenesis and spread.
- Findings suggest novel diagnostic and therapeutic targets for PD and related disorders.
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