Nerve growth factor prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced cell death via the Akt pathway by suppressing caspase-3-like activity using PC12 cells: Relevance to therapeutical application for parkinson's disease

Shimoke, Koji; Chiba, Hayato

doi:10.1002/1097-4547(20010301)63:5<402::aid-jnr1035>3.0.co;2-f

Cited by 89 publications

(43 citation statements)

References 43 publications

(64 reference statements)

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“…Preclinical and clinical findings suggest that neurotrophins are a promising therapy for peripheral neuropathies (McMahon and Priestly, 1995) and neurodegenerative diseases, such as Alzheimer's (Sivanathan and Leavitt, 2005;Tuszynski et al, 2005) and Parkinson's disease (Shimoke and Chiba, 2001). However, neurotrophins do not make good drug candidates because of their poor pharmacokinetic behavior and bioavailability at the desired targets.…”

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confidence: 99%

Neuroprotection by Small Molecule Activators of the Nerve Growth Factor Receptor

Lin¹,

Pirrung²,

Deng³

et al. 2007

J Pharmacol Exp Ther

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There is a great deal of interest in neurotrophin therapy to prevent neuronal degeneration. However, the blood-brain barrier presents a major hurdle in the use of peptide therapeutics. The goal of this study was to identify small molecule, cellpermeable nerve growth factor (NGF) activators. Combinatorial libraries of asterriquinones (Ͼ300) and mono-indolyl-quinones (Ͼ60) were screened using a 96-well enzyme-linked immunosorbent assay that detects phosphorylated TrkA, the NGF receptor. The libraries were also screened for dose-dependent cytotoxicity. From these screens, we generated quantitative structure-activity relationship models for activity and toxicity, and then we selected two compounds, 2-(6-chloro-1H-indol-3-yl)-5-(2-cyclopropyl-1H-indol-3-yl)-3,6-dihydroxy-[1,4]benzoquinone (1H5) and 2,5-dimethoxy-3-(7-fluoro-1H-indol-3-yl)-[1,4]-benzoquinone (5E5), for further study based on high activity and low toxicity. Compound 1H5 (30 M) is an asterriquinone that is a moderate TrkA activator (50% the activity of 100 ng/ml NGF), and it shows little toxicity at concentrations up to 100 M. 1H5 can protect differentiated PC12 neurons from apoptotic cell death induced by NGF withdrawal. Compound 5E5 (30 M) is a mono-indolyl-quinone that is a very strong activator of TrkA (Ͼ200% the activity of 100 ng/ml NGF), and it is nontoxic at concentrations up to 10 M. Activation of TrkA can be detected at 1 M 5E5, and 3 to 10 M 5E5 activates TrkA and extracellular signal-regulated kinase as strongly as a maximal dose of NGF (100 ng/ml). A combination of a low dose of 5E5 (1 M) with a submaximal dose of NGF (10 ng/ml) promotes neuronal differentiation of PC12 cells. These compounds represent a new class of TrkA activators that could have potential utility in the treatment of neurodegenerative diseases.

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confidence: 99%

Neuroprotection by Small Molecule Activators of the Nerve Growth Factor Receptor

Lin¹,

Pirrung²,

Deng³

et al. 2007

J Pharmacol Exp Ther

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“…In addition, an ordinary apoptosis mechanism was also present [4,5]. We also found that GRP78 was upregulated following treatment of the cells with nerve growth factor (NGF), despite NGF promoting cell viability [6,7]. This result suggests that GRP78 may serve as a functional protein in ER stress prevention, as well as a marker of ER stress.…”

Section: Editorialmentioning

confidence: 71%

Epigenetic Regulation by Bisphenol A as a Neuronal Morphogen

Matsuura¹,

Yamazoe²,

Maruoka³

et al. 2017

J Bioengineer & Biomedical Sci

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EditorialSynthetic compounds are having epigenetic or cellular reprogramming impact which is an established truth. Commercial use of such synthetic compounds should be analyzed for health impact on human being before redundant use, especially related to food items. Bisphenol A (BPA) is one such compound which major used in the plastic industry and also for generation of epoxy compounds. There is an abundant use of this compound in packaging industry which includes canning food items. Therefore, thorough investigation is required regarding the impact of the compound on our health. Literature evidence is available related to the harmful effect of Bisphenol A, which generally acts as endocrine disruptors. Moreover, impact of BPA on male and female reproduction, neurological and behavioral issues have been proved earlier. It was found to have carcinogenic activity on human. Such impact is done generally through alteration of the epigenetic regulation of the DNA methylation. Endocrine disrupting chemicals (EDCs) promote a female-inducing phenotype in organs comprised of genital cells. Examples include miniaturized male genitalia and uterine cell death. The effects of EDCs are speculated to be due to their action as female-determinative factors through inhibition of endogenous male hormone receptors. Bisphenol A (BPA) is an endocrine disrupting chemical (EDC) that can cross the brain-brood barrier (BBB) due to its hydrophobic character [1], and thus, neurons or glial cells can be affected in a BPA-specific manner. We have found that EDC which involves alkylphenol group as same as BPA can cause apoptosis in PC12 cells [2]. This mechanism was classified as endoplasmic stress (ER)-mediated apoptosis, due to involvement of accumulation of unfolded proteins and upregulation of glucose-regulated protein 78 (GRP78), a marker of ER stress [3]. In addition, an ordinary apoptosis mechanism was also present [4,5]. We also found that GRP78 was upregulated following treatment of the cells with nerve growth factor (NGF), despite NGF promoting cell viability [6,7]. This result suggests that GRP78 may serve as a functional protein in ER stress prevention, as well as a marker of ER stress. In addition to functional prevention of ER stress-mediated apoptosis, NGF promotes neurite extension in PC12 cells [8]. This phenomenon is necessary for physiological development of the embryo and preservation of mature neurons. Surprisingly, we found that BPA mimicked the function of NGF, suggesting that endogenous hormonal ligands are inhibited by BPA. A morphological analysis showed that the shape of BPA-treated cells was the same as that of forskolin-treated cells (manuscript in preparation). Forskolin promotes neuronal differentiation via the PKA-CREB pathway, in which PKA activated by forskolin phosphorylates CREB, which then binds to CRE sites in various gene promoters (manuscript in preparation). This process also involves specific acetylation of histones, which also induces the expression of nur77 gene, one of the immediate early gene (manu...

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“…45) Recent reports have shown that elevation of ERK1/2 or Akt levels and activities could result in apoptosis inhibition. [46][47][48][49] Therefore, EXD treatment may inhibit the total levels or activities of ERK1/2 and Akt, and then induce HUVEC apoptosis. In addition, changes of ERK1/2 and Akt expression are also observed in many cancers, including hepatocellular cancer, 50,51) colon cancer, 52) breast cancer, 53) Fig.…”

Section: )mentioning

confidence: 99%

Erxian Decoction, a Traditional Chinese Herbal Formula, Inhibits Angiogenesis in Human Umbilical Vein Endothelial Cells

Tong

Huang

et al. 2013

Biological & Pharmaceutical Bulletin

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Our previous study demonstrated that Erxian Decoction (EXD), a traditional Chinese herbal formula, inhibited angiogenesis in zebrafish embryos. To further investigate the anti-angiogenic activity and mechanism of EXD, we evaluated its inhibitory effect on angiogenesis in mammalian endothelial cells in vitro. Cell based assays included proliferation, apoptosis, migration, tube formation and cell cycle analysis. Real-time quantitative polymerase chain reaction (qPCR) and Western blotting were carried out to evaluate the molecular targets and signaling pathways of EXD in human umbilical vein endothelial cells (HUVECs). EXD inhibited proliferation, migration and tube formation in HUVECs. EXD also caused HUVEC apoptosis and cell increase in G 0 /G 1 phase in cell cycle analysis. Furthermore, it decreased the mRNA expressions of vascular endothelial growth factor A (VEGF-A), VEGFR-1 and VEGFR-2 in HUVECs. It also inhibited extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt activation, suggesting the involvement of these signaling pathways in the anti-angiogenic action of EXD in HUVECs. The anti-angiogenic activity of EXD provides new insights to its clinical application and may lead to potential drug development for treating various cancers, especially in menopausal period in the future.Key words angiogenesis; Erxian Decoction; human umbilical vein endothelial cell; vascular endothelial growth factor A Angiogenesis, which is the formation of new blood vessels from existing ones, plays an important role in tumor growth and metastasis.1) New blood vessels are essential for the delivery of oxygen and nutrients to the tumor microenvironment, especially when the tumor volume is 1-2 mm in diameter. 2)Furthermore, the formation of new blood vessels seems critical by providing route for metastasis and thus it is considered as the major cause of cancer mortality.3) These have led to the design of therapeutic strategies including preventing the formation of new vessels called anti-angiogenesis and damaging existing vessels called vascular targeting, toward the tumor vasculature.4) Angiogenesis has been identified as a hallmark of tumor progression, and there is extensive evidence suggesting that anti-angiogenic therapy might be a promising anticancer therapeutic strategy. 5)

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Nerve growth factor prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced cell death via the Akt pathway by suppressing caspase-3-like activity using PC12 cells: Relevance to therapeutical application for parkinson's disease

Cited by 89 publications

References 43 publications

Neuroprotection by Small Molecule Activators of the Nerve Growth Factor Receptor

Neuroprotection by Small Molecule Activators of the Nerve Growth Factor Receptor

Epigenetic Regulation by Bisphenol A as a Neuronal Morphogen

Erxian Decoction, a Traditional Chinese Herbal Formula, Inhibits Angiogenesis in Human Umbilical Vein Endothelial Cells

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