TAPP1 inhibits the differentiation of oligodendrocyte precursor cells via suppressing the Mek/Erk pathway

Neurosci Bull, 2015 · DOI: 10.1007/s12264-015-1537-5 · Published: October 1, 2015

Simple Explanation

Oligodendrocytes (OLs) are glial cells that form myelin sheaths around axons in the central nervous system (CNS). Loss of the myelin sheath in demyelinating and neurodegenerative diseases can lead to severe impairment of movement. Understanding the extracellular signals and intracellular factors that regulate OL differentiation and myelination during development can help to develop novel strategies for enhancing myelin repair in neurological disorders. Here, we report that TAPP1 was selectively expressed in differentiating OL precursor cells (OPCs).

Study Duration

Not specified

Participants

C57BL/6N mice

Evidence Level

Not specified

Key Findings

1
TAPP1 knockdown promoted OL differentiation and myelin gene expression in culture.
2
Conversely, over-expression of TAPP1 in immature OPCs suppressed their differentiation.
3
Moreover, TAPP1 inhibition in OPCs altered the expression of Erk1/2 but not AKT.

Research Summary

In this study, we present the ﬁ rst evidence that the TAPP1 adaptor protein is selectively expressed by differentiating OPCs (Fig. 1). Functional analyses revealed that knockdown of TAPP1 expression in early OPCs by shRNA led to precocious OL differentiation and myelin protein production in vitro (Fig. 3). Conversely, prolonged TAPP1 expression in OLs in vitro inhibited OL differentiation and myelin gene expression, but did not affect the survival and proliferation of OPCs (Figs. 4, 5).

Practical Implications

Negative Regulation of OL Differentiation

TAPP1 functions to negatively regulate OL differentiation, maintaining the undifferentiated state of OPCs at early stages.

Potential Therapeutic Target

Understanding TAPP1's role could lead to novel strategies for enhancing myelin repair in neurological disorders by manipulating its expression or activity.

Mechanism of Action

TAPP1's influence on the Mek/Erk signaling pathway suggests a potential avenue for therapeutic intervention in demyelinating diseases.

Study Limitations

1
The underlying mechanisms are currently unknown, and future studies with genetic approaches are necessary to elucidate the functions of TAPP1 in OL development and axonal myelination.
2
the Erk1/2 but not the PI3K/Akt/mTOR signaling pathway regulates the transition of early progenitors to the immature OL stage
3
our results identify TAPP1 as an important negative regulator of OPC differentiation through the Mek/Erk signaling pathway.

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