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Neural Regen Res. 2020 Jan;15(1):30-35. doi: 10.4103/1673-5374.262679.

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

Author information

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.

Abstract

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 Αβ1-42 and Αβ1-40 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.

KEYWORDS:

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

PMID:
31535639
DOI:
10.4103/1673-5374.262679
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