Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.11.24 (
mitogen-activated protein kinase
)
95,810
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Oligodendrocytes (OLs) are myelin-forming glial cells in the central nervous system (CNS) and their dysfunction causes neuropathies such as demyelinating diseases.
Proteolipid protein 1
(
PLP1
) is an oligodendrocyte myelin-rich tetraspan membrane protein and aberration of the plp1 gene is known to be responsible for dysmyelinating Pelizaeus-Merzbacher disease (PMD). Among previously identified gene alternations, multiplication of the plp1 gene causes increased expression of
PLP1
, resulting in a phenotype with severe dysmyelination in human and also rodent models. Yet little is known about the relationship between increased
PLP1
expression and oligodendrocyte precursor cell (OPC) differentiation and the intracellular molecular mechanism. Here we show that expression of
PLP1
in OPCs markedly inhibits their differentiation, and that this inhibitory effect is effectively improved by inhibition of
extracellular signal-regulated kinase
(
ERK
) activity. Furthermore, in cocultures with dorsal root ganglion (DRG) neurons,
ERK
inhibition also improves
PLP1
-induced dysmyelination. Thus,
ERK
inhibition helps to improve defective OPC differentiation induced by
PLP1
expression, suggesting that molecules belonging to
ERK
signaling cascade may be new PMD therapeutic targets.
...
PMID:Pelizaeus-Merzbacher disease-associated proteolipid protein 1 inhibits oligodendrocyte precursor cell differentiation via extracellular-signal regulated kinase signaling. 2275 1
