Related Experiment Video
Updated: Jun 9, 2026
Preparation of Rat Oligodendrocyte Progenitor Cultures and Quantification of Oligodendrogenesis Using Dual-infrared Fluorescence Scanning
Published on: February 17, 2016
Tubulin polymerization promoting protein (TPPP/p25) as a marker for oligodendroglial changes in multiple sclerosis
Romana Höftberger1, Stephanie Fink, Fahmy Aboul-Enein
1Institute of Neurology, Medical University of Vienna, Vienna, Austria.
Abstract:
Multiple sclerosis (MS) is an idiopathic chronic inflammatory demyelinating disease of the central nervous system with variable extent of remyelination. Remyelination originates from oligodendrocyte (OG) precursor cells, which migrate and differentiate into mature OG. Tubulin polymerization promoting protein (TPPP/p25) is located in mature OG and aggregates in oligodendroglial cytoplasmic inclusions in multiple system atrophy. We developed a novel monoclonal anti-TPPP/p25 antibody to quantify OG in different subtypes and disease stages of MS, and possible degenerative changes in OG. We evaluated autopsy material from 25 MS cases, including acute, primary progressive, secondary progressive, relapsing remitting MS, and five controls. Demyelinated lesions revealed loss of TPPP/p25-positive OG within the plaques. In remyelination, TPPP/p25 was first expressed in OG cytoplasms and later became positive in myelin sheaths. We observed increased numbers of TPPP/p25 immunoreactive OG in the normal appearing white matter (NAWM) in MS patients. In MS cases, the cytoplasmic area of TPPP/p25 immunoreactivity in the OG was higher in the periplaque area when compared with NAWM and the plaque, and TPPP/p25 immunoreactive OG cytoplasmic area inversely correlated with the disease duration. There was a lack of phospho-TDP-43, phospho-tau, α-synuclein, and ubiquitin immunoreactivity in OG with enlarged cytoplasm. Our data suggest impaired differentiation, migration, and activation capacity of OG in later disease stages of MS. Upregulation of TPPP/p25 in the periplaque white matter OG without evidence for inclusion body formation might reflect an activation state. Distinct and increased expression of TPPP/p25 in MS renders it a potential prognostic and diagnostic marker of MS.
Insights
Tubulin polymerization promoting protein (TPPP/p25) is upregulated in multiple sclerosis (MS) white matter, indicating impaired oligodendrocyte precursor cell function. This suggests TPPP/p25 may serve as a diagnostic marker for MS progression.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease affecting the central nervous system.
- Remyelination in MS involves oligodendrocyte precursor cells (OGCs) differentiating into mature oligodendrocytes (OGs).
- Tubulin polymerization promoting protein (TPPP/p25) is found in mature OGs and is implicated in oligodendroglial cytoplasmic inclusions.
Purpose of the Study:
- To develop a novel monoclonal antibody against TPPP/p25 for quantifying OGs in MS.
- To investigate OG changes and TPPP/p25 expression in various MS subtypes and disease stages.
- To explore TPPP/p25 as a potential diagnostic and prognostic marker for MS.
Main Methods:
- Evaluation of autopsy brain tissue from 25 MS cases and 5 controls.
- Immunohistochemical analysis using a novel anti-TPPP/p25 antibody.
- Quantification of TPPP/p25-positive OGs and assessment of cytoplasmic area and immunoreactivity.
Main Results:
- Loss of TPPP/p25-positive OGs observed in demyelinated MS lesions.
- TPPP/p25 expression initially in OG cytoplasm during remyelination, later in myelin sheaths.
- Increased TPPP/p25-immunoreactive OGs found in normal-appearing white matter (NAWM) of MS patients.
- Enlarged TPPP/p25-positive OG cytoplasmic area in periplaque regions compared to NAWM and plaques.
- TPPP/p25 immunoreactive OG cytoplasmic area inversely correlated with disease duration.
- Absence of specific protein aggregates (phospho-TDP-43, phospho-tau, α-synuclein, ubiquitin) in enlarged OG cytoplasm.
Conclusions:
- Data suggest impaired differentiation, migration, and activation of OGs in later MS stages.
- Upregulation of TPPP/p25 in periplaque white matter OGs may indicate an activation state.
- Distinct and increased TPPP/p25 expression in MS highlights its potential as a prognostic and diagnostic marker.
Related Concept Videos
01:42Microtubule Associated Proteins (MAPs)
01:15Drugs that Stabilize Microtubules