中国神经再生研究（英文版）Issue(1)：30-35,6.DOI:10.4103/1673-5374.262679
Highlights of ASS234: a novel and promising therapeutic agent for Alzheimer’s disease therapy
Alejandro Romero 1José Marco-Contelles 2Eva Ramos1
作者信息
- 1. Department of Pharmacology & Toxicology, Faculty of Veterinary Medicine, Complutense University of Madrid, Madrid, Spain
- 2. Laboratory of Medicinal Chemistry, Institute of General Organic Chemistry (CSIC) Madrid, Spain
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摘要
Abstract
There is no effective treatment to face Alzheimer’s disease complexity. Multitarget molecules are a good ap-proach against the multiple physiopathological events associated with its development and progression. In this context, N-((5-(3-(1-benzylpiperidin-4-yl) propoxy)-1- methyl-1H-indol-2-yl)methyl)-N-methylprop-2-yn-1-amine (ASS234) has been tested achieving promising results. ASS234 has demonstrated to cross the blood-brain barrier in vivo, and a good in silico safety profile being less toxic than donepezil. Besides, ASS234 reversibly inhibits human acetyl- and butyryl-cholinesterase, and irreversibly inhibits human monoamine oxidase A and B. Moreover, this multitarget molecule has antioxidant and neuroprotective properties, and inhibits Aβ1–42 and Aβ1–40 self-aggregation. Inquiring about the mechanism of action, sev-eral signaling pathways related to Alzheimer’s disease had been explored showing that ASS234 induces the wingless-type MMTV integration site (Wnt) family and several members of the heat shock proteins family and moreover counteracts neuroinflammatory and oxidative stress-related genes promoting the induction of several key antioxidant genes. Finally, in vivo experiments with ASS234 in C57BL/6J mice displayed its ability to reduce amyloid plaque burden and gliosis in the cortex and hippocampus, ameliorating sco-polamine-induced learning deficits. Here we gather the information regarding ASS234 evaluated so far, showing its ability to face different targets, necessary to counteract a neurodegenerative disease as complex as the Alzheimer’s disease.关键词
AChE/ BuChE/ gene expression/ heat shock proteins/ inflammation/ in silico toxicology/ MAO A/B/neuroprotection/ oxidative stress/ Wnt signalingKey words
AChE/ BuChE/ gene expression/ heat shock proteins/ inflammation/ in silico toxicology/ MAO A/B/neuroprotection/ oxidative stress/ Wnt signaling引用本文复制引用
Alejandro Romero,José Marco-Contelles,Eva Ramos..Highlights of ASS234: a novel and promising therapeutic agent for Alzheimer’s disease therapy[J].中国神经再生研究（英文版）,2020,(1):30-35,6.
