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oai:docta.ucm.es:20.500.14352/1204012025-05-22T23:46:37Zcom_20.500.14352_14col_20.500.14352_15

Highlights of ASS234: a novel and promising therapeutic agent for Alzheimer's disease therapy. Romero Martínez, Manuel Alejandro Marco Contelles, José Luis Ramos Alonso, Eva 615.01/.03 AChE BuChE MAO A/B Wnt signaling Gene expression Heat shock proteins In silico toxicology Inflammation Neuroprotection Oxidative stress Ciencias Biomédicas Farmacología (Medicina) 32 Ciencias Médicas 3209 Farmacología 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 inhibits Αβ and Αβ 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. Sección Deptal. de Farmacología y Toxicología (Veterinaria) Fac. de Veterinaria TRUE pub 2025-05-22T14:19:23Z 2025-05-22T14:19:23Z 2020-01 journal article VoR https://hdl.handle.net/20.500.14352/120401 1673-5374 10.4103/1673-5374.262679 1876-7958 eng Romero, A., Marco-Contelles, J., & Ramos, E. (2020). Highlights of ASS234: a novel and promising therapeutic agent for Alzheimer's disease therapy. Neural regeneration research, 15(1), 30–35. https://doi.org/10.4103/1673-5374.262679 Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ open access application/pdf Medknow Publications