Prenylated quinolinecarboxylic acid derivative prevents neuronal cell death through inhibition of MKK4

Ogura, Masato; Kikuchi, Haruhisa; Shakespear, Norshalena; Suzuki, Toshiyuki; Yamaki, Junko; Homma, Miwako K.; Oshima, Yoshiteru; Homma, Yoshimi

doi:10.1016/j.bcp.2018.10.008

Cited by 10 publications

(9 citation statements)

References 52 publications

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“…Furthermore, Ppc-1 and its derivative, PQA-18 (Figure 11A), suppress IL-2 production in Jurkat T cells in vitro [114]. Another Ppc-1 derivative, PQA-11 (Figure 11A), has potent neuroprotective activities in vitro and in vivo, possibly via the inhibition of mitogen-activated protein kinase kinase 4 (MKK4) [115].…”

Section: Novel Biologically Active Compounds Found In Cellular Slimentioning

confidence: 99%

Dictyostelium: An Important Source of Structural and Functional Diversity in Drug Discovery

Kubohara

Kikuchi

2018

Cells

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The cellular slime mold Dictyostelium discoideum is an excellent model organism for the study of cell and developmental biology because of its simple life cycle and ease of use. Recent findings suggest that Dictyostelium and possibly other genera of cellular slime molds, are potential sources of novel lead compounds for pharmacological and medical research. In this review, we present supporting evidence that cellular slime molds are an untapped source of lead compounds by examining the discovery and functions of polyketide differentiation-inducing factor-1, a compound that was originally isolated as an inducer of stalk-cell differentiation in D. discoideum and, together with its derivatives, is now a promising lead compound for drug discovery in several areas. We also review other novel compounds, including secondary metabolites, that have been isolated from cellular slime molds.

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Section: Novel Biologically Active Compounds Found In Cellular Slimentioning

confidence: 99%

Dictyostelium: An Important Source of Structural and Functional Diversity in Drug Discovery

Kubohara

Kikuchi

2018

Cells

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“…Mitogenactivated kinase-kinase 4 (MKK4) is involved in the mechanism of PD-related cell death (Saporito et al, 2000). Ogura et al demonstrated that MKK4 inhibition could rescue cells from cell death, indicating that MKK4 played an important role in MPP + -induced cell death and possibly in PD pathogenesis (Ogura et al, 2019). miR-200a-3p targeted MKK4 by binding to two independent sites on the 3'-untranslated region of dual-specificity MKK4 (Map2k4)/MKK4 mRNA.…”

Section: Involvement Of Mirnas In Astrocyte Dysfunction In Pdmentioning

confidence: 99%

Involvement of Astrocytes and microRNA Dysregulation in Neurodegenerative Diseases: From Pathogenesis to Therapeutic Potential

Bai

Piao

et al. 2021

Front. Mol. Neurosci.

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Astrocytes are the most widely distributed and abundant glial cells in the central nervous system (CNS). Neurodegenerative diseases (NDDs) are a class of diseases with a slow onset, progressive progression, and poor prognosis. Common clinical NDDs include Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD). Although these diseases have different etiologies, they are all associated with neuronal loss and pathological dysfunction. Accumulating evidence indicates that neurotransmitters, neurotrophic factors, and toxic metabolites that are produced and released by activated astrocytes affect and regulate the function of neurons at the receptor, ion channel, antigen transfer, and gene transcription levels in the pathogenesis of NDDs. MicroRNAs (miRNAs) are a group of small non-coding RNAs that play a wide range of biological roles by regulating the transcription and post-transcriptional translation of target mRNAs to induce target gene expression and silencing. Recent studies have shown that miRNAs participate in the pathogenesis of NDDs by regulating astrocyte function through different mechanisms and may be potential targets for the treatment of NDDs. Here, we review studies of the role of astrocytes in the pathogenesis of NDDs and discuss possible mechanisms of miRNAs in the regulation of astrocyte function, suggesting that miRNAs may be targeted as a novel approach for the treatment of NDDs.

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“…Cellular slime molds are soil microorganisms that produce many pharmacologically active molecules and are an important source of lead compounds for medical research [17][18][19][20][21][22]. We have previously identified prenylated quinolinecarboxylic acid (PQA)-18, as a novel immunosuppressant with p21-activated kinase 2 (PAK2) inhibitory activity, from a group of slime mold-derived PQA derivative [21].…”

Section: Introductionmentioning

confidence: 99%

Prenylated quinolinecarboxylic acid compound-18 prevents sensory nerve fiber outgrowth through inhibition of the interleukin-31 pathway

et al. 2021

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Interleukin-31 (IL-31) is involved in excessive development of cutaneous sensory nerves in atopic dermatitis (AD), leading to severe pruritus. We previously reported that PQA-18, a prenylated quinolinecarboxylic acid (PQA) derivative, is an immunosuppressant with inhibition of p21-activated kinase 2 (PAK2) and improves skin lesions in Nc/Nga mice as an AD model. In the present study, we investigate the effect of PQA-18 on sensory nerves in lesional skin. PQA-18 alleviates cutaneous nerve fiber density in the skin of Nc/Nga mice. PQA-18 also inhibits IL-31-induced sensory nerve fiber outgrowth in dorsal root ganglion cultures. Signaling analysis reveals that PQA-18 suppresses phosphorylation of PAK2, Janus kinase 2, and signal transducer and activator of transcription 3 (STAT3), activated by IL-31 receptor (IL-31R), resulting in inhibition of neurite outgrowth in Neuro2A cells. Gene silencing analysis for PAK2 confirms the requirement for STAT3 phosphorylation and neurite outgrowth elicited by IL-31R activation. LC/MS/MS analysis reveals that PQA-18 prevents the formation of PAK2 activation complexes induced by IL-31R activation. These results suggest that PQA-18 inhibits the IL-31 pathway through suppressing PAK2 activity, which suppresses sensory nerve outgrowth. PQA-18 may be a valuable lead for the development of a novel drug for pruritus of AD.

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Prenylated quinolinecarboxylic acid derivative prevents neuronal cell death through inhibition of MKK4

Cited by 10 publications

References 52 publications

Dictyostelium: An Important Source of Structural and Functional Diversity in Drug Discovery

Dictyostelium: An Important Source of Structural and Functional Diversity in Drug Discovery

Involvement of Astrocytes and microRNA Dysregulation in Neurodegenerative Diseases: From Pathogenesis to Therapeutic Potential

Prenylated quinolinecarboxylic acid compound-18 prevents sensory nerve fiber outgrowth through inhibition of the interleukin-31 pathway

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