Related Experiment Video
Updated: Aug 14, 2026
Sequential Extraction of Soluble and Insoluble Alpha-Synuclein from Parkinsonian Brains
Published on: January 5, 2016
Immunoexpression of 14-3-3 proteins in glial cytoplasmic inclusions of multiple system atrophy
Takashi Komori1, Keisuke Ishizawa, Nobutaka Arai
1Department of Clinical Neuropathology, Tokyo Metropolitan Institute for Neuroscience, 2-6 Musashidai, Fuchu City, 183-8526 Tokyo, Japan. komori@tmin.ac.jp
Abstract:
Glial cytoplasmic inclusions (GCIs) are the histological hallmark of multiple system atrophy (MSA). In six postmortem brains of patients with MSA, 14-3-3-protein immunoreactivity was identified in GCIs predominately in the white matter tissue of the basal forebrain and cerebellum. Using double immunohistochemistry, co-localization of 14-3-3-protein and alpha-synuclein immunoreactivities in the GCIs was confirmed. The immunolabeling rate of GCIs with 14-3-3 proteins varied regionally from approximately 40% to 90%. Semiquantitative analysis yielded a significant negative correlation between degree of tissue degeneration and density of 14-3-3-protein-immunoreactive GCIs. The 14-3-3 proteins are active cofactors involved in cellular regulation through binding to phosphorylated motifs in target proteins and alpha-synuclein is a known target of 14-3-3. Our study suggests that 14-3-3 proteins are closely associated with alpha-synuclein in GCIs and 14-3-3 proteins may be candidate cofactors of alpha-synuclein in GCI formation.
Insights
14-3-3 proteins are closely associated with alpha-synuclein in glial cytoplasmic inclusions (GCIs) in multiple system atrophy (MSA). These proteins may act as cofactors in GCI formation, a key feature of MSA pathology.
Area of Science:
- Neuroscience
- Pathology
- Biochemistry
Background:
- Glial cytoplasmic inclusions (GCIs) are the defining histological feature of multiple system atrophy (MSA).
- The precise molecular mechanisms underlying GCI formation in MSA remain incompletely understood.
Purpose of the Study:
- To investigate the presence and role of 14-3-3 proteins in GCIs within MSA brains.
- To explore the relationship between 14-3-3 proteins, alpha-synuclein, and neurodegeneration in MSA.
Main Methods:
- Postmortem brain tissue analysis from six MSA patients.
- Immunohistochemistry and double immunohistochemistry to detect 14-3-3 and alpha-synuclein.
- Semiquantitative analysis of GCI density and correlation with tissue degeneration.
Main Results:
- 14-3-3 protein immunoreactivity was found in GCIs, particularly in the basal forebrain and cerebellum.
- Co-localization of 14-3-3 proteins and alpha-synuclein within GCIs was confirmed.
- A negative correlation was observed between tissue degeneration and the density of 14-3-3-immunoreactive GCIs.
Conclusions:
- 14-3-3 proteins are closely associated with alpha-synuclein in GCIs in MSA.
- 14-3-3 proteins are potential cofactors in the formation of GCIs, contributing to MSA pathogenesis.
More Related Videos
09:16Exogenous Administration of Microsomes-associated Alpha-synuclein Aggregates to Primary Neurons As a Powerful Cell Model of Fibrils Formation
Published on: June 26, 2018
06:02Experimental Approaches for Biochemical Analysis of Glial Fibrillary Acidic Protein and Its Disease-associated Variants
Published on: November 28, 2025
