The possibility to target MAPK/ERK in developing and/or refining pharmacological approaches to treat psychiatric disorders in which fear regulation is defective has also been envisaged.
Pharmacological targeting of ERK reversed dendritic alterations associated with dp/+ neurons, outlining a strategy for the analysis and reversal of cellular phenotypes in CNV-related psychiatric disorders.
The demonstration of a pathogenic role for p38 activation may lead to the development of therapeutic strategies for BSS and related conditions, such as acanthosis nigricans or craniosynostosis.
These observations suggest that suppression of these molecules, which are involved in the TLR4-MyD88 pathway and the downstream p38 MAPK and NF-kappaB pathways, should be beneficial to prevent development of AIDS in HIV-1-infected people.
HE-staining, Immunohistochemical, Western blot and Enzyme Linked Immunosorbent Assay were applied to examine the clinicopathologic feature of AK and the change of p38 MAPK signal pathway treated with astraglin under the condition of UVB in vitro and in vivo.
In addition, RNA interference (RNAi)-mediated suppression of SHIP-1 in erythroleukemia cells activates the phosphatidylinositol 3-kinase (PI 3-K) and extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathways, blocks erythroid differentiation, accelerates erythropoietin-induced proliferation, and leads to PI 3-K-dependent Fli-1 up-regulation.
These results provide a possible underlying molecular mechanism to explain the association between reduced MIR335 with poor clinical outcome, and suggest that approaches to re-introduce MIR335 expression or override MAPK1 activity may offer promising therapeutic strategies in the treatment of ALL.
The Bcl-2/Bcl-xL/Bax and the Ras/Raf/MEK/ERK (MAPK) pathways are often deregulated in many human cancers and especially in acute lymphoblastic leukemia and acute myeloid leukemia.
In HL-60 human myeloblastic leukemia cells, retinoic acid is known to cause cFMS, RAF, MEK, and ERK2 dependent myeloid cell differentiation and G0 arrest associated with RB tumor suppressor protein hypophosphorylation, implicating receptor tyrosine kinase signal transduction in propelling these retinoic acid-induced cellular effects.
Using acute myocardial infarction rat models, we found that a combination therapy of CaSR inhibition and embryonic stem cell (ESC) transplantation after acute myocardial infarction (AMI) leads to a dramatic reduction in the infarct size; a significant increase in the maximum rising and falling rate (+dp/dtmax and -dp/dtmax, respectively) of left ventricular pressure; a significant decrease in left ventricular end-diastolic pressure; a significant decrease in the mRNA expression level of CaSR, Bax, Bcl-2, cleaved caspase-3, cleaved caspase-9, p-ERK, p-JNK and p-P38 protein together with apoptosis indexes in the C and E groups; and a significant decrease in cTnT levels as well as LDH and CK activity.
The results of in vivo assays demonstrated that Ginkgo biloba extract prevents AMI and suppresses inflammation‑ and apoptosis‑regulating p38 MAPK, NF‑κB and Bcl‑2 signaling pathways.