Highlights of ASS234: a novel and promising therapeutic agent for Alzheimer’s disease therapy

作     者：Alejandro Romero JoséMarco-Contelles Eva Ramos Alejandro Romero;José Marco-Contelles;Eva Ramos

作者机构：Department of Pharmacology&ToxicologyFaculty of Veterinary MedicineComplutense University of MadridMadridSpain Laboratory of Medicinal ChemistryInstitute of General Organic Chemistry(CSIC)MadridSpain 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2020年第15卷第1期

页      面：30-35页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

主　　题：AChE BuChE gene expression heat shock proteins inflammation in silico toxicology MAO A/B neuroprotection oxidative stress Wnt signaling 

摘      要：There is no effective treatment to face Alzheimer’s disease complexity.Multitarget molecules are a good approach 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 inhibitsΑβ1–42 andΑβ1–40 self-aggregation.Inquiring about the mechanism of action,several 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 scopolamine-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.