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Wnt signaling pathway, a potential target for Alzheimer's disease treatment, is activated by a novel multitarget compound ASS234.Wnt信号通路是阿尔茨海默病治疗的一个潜在靶点，被一种新型多靶点化合物ASS234激活。
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Multipotent, permeable drug ASS234 inhibits Aβ aggregation, possesses antioxidant properties and protects from Aβ-induced apoptosis in vitro.多功能、可渗透的药物 ASS234 抑制 Aβ 聚集，具有抗氧化特性，并能防止体外 Aβ 诱导的细胞凋亡。
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In silico assessment of the metabolism and its safety significance of multitarget propargylamine ASS234.多靶点炔丙胺ASS234代谢及其安全性意义的计算机模拟评估
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Aberrant DNA methylation associated with Alzheimer's disease in the superior temporal gyrus.与颞上回阿尔茨海默病相关的异常DNA甲基化。
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The proof-of-concept of ASS234: Peripherally administered ASS234 enters the central nervous system and reduces pathology in a male mouse model of Alzheimer disease.ASS234的概念验证：经外周给药的ASS234进入中枢神经系统，并减轻阿尔茨海默病雄性小鼠模型中的病理变化。
J Psychiatry Neurosci. 2017 Jan;42(1):59-69. doi: 10.1503/jpn.150209.
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ASS234, As a New Multi-Target Directed Propargylamine for Alzheimer's Disease Therapy.ASS234，一种用于阿尔茨海默病治疗的新型多靶点导向炔丙胺。
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One for All? Hitting Multiple Alzheimer's Disease Targets with One Drug.一药多用？用一种药物攻克多个阿尔茨海默病靶点。
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本文引用的文献

1
In vivo activation of Wnt signaling pathway enhances cognitive function of adult mice and reverses cognitive deficits in an Alzheimer's disease model.体内激活 Wnt 信号通路可增强成年小鼠的认知功能，并逆转阿尔茨海默病模型中的认知缺陷。
J Neurosci. 2014 Feb 5;34(6):2191-202. doi: 10.1523/JNEUROSCI.0862-13.2014.
2
Multipotent, permeable drug ASS234 inhibits Aβ aggregation, possesses antioxidant properties and protects from Aβ-induced apoptosis in vitro.多功能、可渗透的药物 ASS234 抑制 Aβ 聚集，具有抗氧化特性，并能防止体外 Aβ 诱导的细胞凋亡。
Curr Alzheimer Res. 2013 Oct;10(8):797-808. doi: 10.2174/15672050113109990151.
3
Effects of novel monoamine oxidases and cholinesterases targeting compounds on brain neurotransmitters and behavior in rat model of vascular dementia.新型单胺氧化酶和胆碱酯酶靶向化合物对血管性痴呆大鼠模型脑神经递质和行为的影响。
Curr Pharm Des. 2014;20(2):161-71. doi: 10.2174/13816128113199990026.
4
Wnt signaling: role in Alzheimer disease and schizophrenia.Wnt 信号通路：在阿尔茨海默病和精神分裂症中的作用。
J Neuroimmune Pharmacol. 2012 Dec;7(4):788-807. doi: 10.1007/s11481-012-9417-5. Epub 2012 Nov 18.
5
Synthesis, biological evaluation, and molecular modeling of donepezil and N-[(5-(benzyloxy)-1-methyl-1H-indol-2-yl)methyl]-N-methylprop-2-yn-1-amine hybrids as new multipotent cholinesterase/monoamine oxidase inhibitors for the treatment of Alzheimer's disease.多奈哌齐和 N-[(5-(苄氧基)-1-甲基-1H-吲哚-2-基)甲基]-N-甲基丙-2-炔-1-胺杂合体的合成、生物评价和分子模拟作为治疗阿尔茨海默病的新型多效胆碱酯酶/单胺氧化酶抑制剂。
J Med Chem. 2011 Dec 22;54(24):8251-70. doi: 10.1021/jm200853t. Epub 2011 Nov 15.
6
Transcriptional up-regulation of antioxidant genes by PPARδ inhibits angiotensin II-induced premature senescence in vascular smooth muscle cells.过氧化物酶体增殖物激活受体 δ 通过转录激活抗氧化基因抑制血管平滑肌细胞中血管紧张素Ⅱ诱导的过早衰老。
Biochem Biophys Res Commun. 2011 Mar 25;406(4):564-9. doi: 10.1016/j.bbrc.2011.02.091. Epub 2011 Feb 23.
7
Wnt signaling in neuroprotection and stem cell differentiation.Wnt信号通路在神经保护和干细胞分化中的作用
Prog Neurobiol. 2008 Nov;86(3):281-96. doi: 10.1016/j.pneurobio.2008.08.001. Epub 2008 Aug 19.
8
The Wnt signaling pathway: aging gracefully as a protectionist?Wnt信号通路：作为一种保护机制而优雅地衰老？
Pharmacol Ther. 2008 Apr;118(1):58-81. doi: 10.1016/j.pharmthera.2008.01.004. Epub 2008 Feb 11.
9
Acetylcholinesterase (AChE)--amyloid-beta-peptide complexes in Alzheimer's disease. the Wnt signaling pathway.阿尔茨海默病中的乙酰胆碱酯酶（AChE）-β淀粉样肽复合物。Wnt信号通路。
Curr Alzheimer Res. 2004 Nov;1(4):249-54. doi: 10.2174/1567205043332063.
10
Acetylcholinesterase-Abeta complexes are more toxic than Abeta fibrils in rat hippocampus: effect on rat beta-amyloid aggregation, laminin expression, reactive astrocytosis, and neuronal cell loss.乙酰胆碱酯酶 - β淀粉样蛋白复合物在大鼠海马体中比β淀粉样蛋白原纤维毒性更强：对大鼠β淀粉样蛋白聚集、层粘连蛋白表达、反应性星形胶质细胞增生和神经元细胞丢失的影响。
Am J Pathol. 2004 Jun;164(6):2163-74. doi: 10.1016/s0002-9440(10)63774-1.

Wnt signaling pathway, a potential target for Alzheimer's disease treatment, is activated by a novel multitarget compound ASS234.

作者信息

del Pino Javier, Ramos Eva, Aguilera Oscar M Bautista, Marco-Contelles José, Romero Alejandro

机构信息

Departamento de Toxicología y Farmacología, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain.

出版信息

CNS Neurosci Ther. 2014 Jun;20(6):568-70. doi: 10.1111/cns.12269. Epub 2014 Apr 8.

DOI:10.1111/cns.12269
PMID:24712554
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6493027/
Abstract
摘要