Discovery of a novel neuroprotectant, BHDPC, that protects against MPP+/MPTP-induced neuronal death in multiple experimental models

Chong, Cheong-Meng; Ma, Dan; Zhao, Chao; Franklin, Robin J.M.; Zhou, Zhong-Yan; Ai, Nana; Li, Chuwen; Yu, Huidong; Hou, Tingjun; Sa, Fei; Lee, Simon Ming‐Yuen

doi:10.1016/j.freeradbiomed.2015.08.013

Cited by 22 publications

(26 citation statements)

References 49 publications

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“…Thus, the two pathways may be key targets in therapy for neurodegenerative disease. This possibility is also proposed by using Parkinson's disease model [17]. However, some hereditary diseases, for instance, huntinton's disease cannot be cured because responsible gene is continued to express.…”

Section: Resultsmentioning

confidence: 99%

Genomic Control of Upregulation of GRP78 Expression for Promotion of Neurite Elongation and Attenuation of Cell Death via PKA-Mediated Signaling in PC12 Cells

Yamazoe¹,

Nishihata²,

Nakagawa³

2015

Clin Pharmacol Biopharm

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Neurodegeneration occurs due to neuronal cell death and subsequently disrupts neuronal networks. In current medicine, methods for interruption of neuronal cell death and avoidance of disruption of neuronal networks have potential as therapy for neurodegenerative disorders. Development of this therapy requires analysis of the molecular mechanism of neurite extension that leads to network formation. Here, we show that forskolin (fsk), an activator of adenylate cyclase, increases the intracellular cAMP concentration and induces neurite outgrowth in PC12 cells. The effect of fsk on neurite outgrowth was diminished by H89, an inhibitor of protein kinase A (PKA), and by PD98059 and U0126, which are inhibitors of the mitogen-activated protein kinase (MAPK) signaling pathway. With fsk treatment in the presence of tunicamycin, an inducer of cell death, the activity of the glucose-regulated protein 78 (GRP78) promoters was upregulated. Interestingly, this effect was completely abolished by H89 and by PD98059 and U0126. This phenomenon was confirmed using a dominant-negative PKA-expressing PC12 cell line, in which the PKA-mediated signaling pathway was completely eliminated. These lines of evidence suggest that GRP78 promotes neuronal elongation that is regulated by fsk and mediated by PKA.

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Section: Resultsmentioning

confidence: 99%

Genomic Control of Upregulation of GRP78 Expression for Promotion of Neurite Elongation and Attenuation of Cell Death via PKA-Mediated Signaling in PC12 Cells

Yamazoe¹,

Nishihata²,

Nakagawa³

2015

Clin Pharmacol Biopharm

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“…Male C57BL/6J mice (9-week old) were obtained from CLEA Japan (Tokyo, Japan), and housed at 21°C with a 12:12h light/dark cycle with free access to water and a commercial diet. MPTP was used to induce Parkinsonism in animal models [25]. After preliminary breeding for one week, mice were treated with vehicle (0.1% DMSO), PQA-11 (0.5 mg/kg), or SP600125 (1.0 mg/kg) by intraperitoneal injection three times a week for two weeks.…”

Section: Animal Studymentioning

confidence: 99%

“…After preliminary breeding for one week, mice were treated with vehicle (0.1% DMSO), PQA-11 (0.5 mg/kg), or SP600125 (1.0 mg/kg) by intraperitoneal injection three times a week for two weeks. MPTP (20 mg/kg) or PBS (control) was administered four times at 2 h intervals on Day 1 of the second week [25].…”

Section: Animal Studymentioning

confidence: 99%

“…The above results led us to examine the pharmacological profiles of PQA-11, using in vitro models of PD and AD, that is, SH-SY5Y human neuroblastoma cells treated with MPP + and Aβ1-42, respectively [18,25,27] 21.5±2.1% ## ; **p<0.01, as compared with control; # p<0.05, ## p<0.01, as compared with MPP + ; one-way ANOVA with Tukey-Kramer post hoc comparisons] ( Fig. 2A).…”

Section: Inhibition Of Mpp + -And Aβ1-42-induced Cell Death By Pqa-11mentioning

confidence: 99%

“…The MPTP model was employed for the assessment of the neuroprotective effects of PQA-11 in vivo [25,34]. C57BL/6J mice were administered with MPTP to induce degeneration in nigrostriatal dopaminergic neurons, and treated with a vehicle (0.1% DMSO), PQA-11 (0.5 mg/kg) or SP600125 (1.0 mg/kg), three times a week by intraperitoneal administration.…”

Section: Alleviation Of Mptp-induced Neurodegeneration By Pqa-11mentioning

confidence: 99%

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

Ogura

Kikuchi

Shakespear

et al. 2019

Biochemical Pharmacology

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The development of neuroprotective agents is necessary for the treatment of neurodegenerative diseases. Here, we report PQA-11, a prenylated quinolinecarboxylic acid (PQA) derivative, as a potent neuroprotectant. PQA-11 inhibits glutamate-induced cell death and caspase-3 activation in hippocampal cultures, as well as inhibits N-Methyl-4phenylpyridinium iodide-and amyloid β1-42-induced cell death in SH-SY5Y cells. PQA-11 also suppresses mitogen-activated protein kinase kinase 4 (MKK4) and c-jun N-terminal kinase (JNK) signaling activated by these neurotoxins. Quartz crystal microbalance analysis and in vitro kinase assay reveal that PQA-11 interacts with MKK4, and inhibits its sphingosine-induced activation. The administration of PQA-11 by intraperitoneal injection alleviates 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced degeneration of nigrostriatal dopaminergic neurons in mice. These results suggest that PQA-11 is a unique MKK4 inhibitor with potent neuroprotective effects in vitro and in vivo. PQA-11 may be a valuable lead for the development of novel neuroprotectants.

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Biologically active compounds and drugs in the tetrazole series

Мызников

Ворона

Zevatskii

2021

Chem Heterocycl Comp

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Discovery of a novel neuroprotectant, BHDPC, that protects against MPP+/MPTP-induced neuronal death in multiple experimental models

Cited by 22 publications

References 49 publications

Genomic Control of Upregulation of GRP78 Expression for Promotion of Neurite Elongation and Attenuation of Cell Death via PKA-Mediated Signaling in PC12 Cells

Genomic Control of Upregulation of GRP78 Expression for Promotion of Neurite Elongation and Attenuation of Cell Death via PKA-Mediated Signaling in PC12 Cells

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

Biologically active compounds and drugs in the tetrazole series

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