3-[[(3S)-1,2,3,4-Tetrahydroisoquinoline-3-Carbonyl]Amino]Propanoic Acid (THICAPA) Is Protective Against Aβ42-Induced Toxicity In Vitro and in an Alzheimer's Disease Drosophila.

Autor:	Tan FHP; School of Health Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.; USM-RIKEN Interdisciplinary Centre for Advanced Sciences (URICAS), Universiti Sains Malaysia, Penang, Malaysia., Ting ACJ; School of Biological Sciences, Universiti Sains Malaysia, Penang, Malaysia., Najimudin N; USM-RIKEN Interdisciplinary Centre for Advanced Sciences (URICAS), Universiti Sains Malaysia, Penang, Malaysia.; School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia., Watanabe N; USM-RIKEN Interdisciplinary Centre for Advanced Sciences (URICAS), Universiti Sains Malaysia, Penang, Malaysia.; Bioprobe Application Research Unit, RIKEN CSRS, Wako, Saitama, Japan., Shamsuddin S; School of Health Sciences, Universiti Sains Malaysia, Kelantan, Malaysia.; Nanobiotech Research Initiative, Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, Penang, Malaysia., Zainuddin A; Department of Chemical Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia., Osada H; USM-RIKEN Interdisciplinary Centre for Advanced Sciences (URICAS), Universiti Sains Malaysia, Penang, Malaysia.; Chemical Biology Research Group, RIKEN CSRS, Wako, Saitama, Japan., Azzam G; School of Biological Sciences, Universiti Sains Malaysia, Penang, Malaysia.; Malaysia Genome and Vaccine Institute (MGVI), National Institutes of Biotechnology Malaysia (NIBM), Jalan Bangi, Selangor, Malaysia.
Jazyk:	angličtina
Zdroj:	The journals of gerontology. Series A, Biological sciences and medical sciences [J Gerontol A Biol Sci Med Sci] 2023 Oct 28; Vol. 78 (11), pp. 1944-1952.
DOI:	10.1093/gerona/glad169
Abstrakt:	Alzheimer's disease (AD) is the most prevalent type of dementia globally. The accumulation of amyloid-beta (Aβ) extracellular senile plaques in the brain is one of the hallmark mechanisms found in AD. Aβ42 is the most damaging and aggressively aggregating Aβ isomer produced in the brain. Although Aβ42 has been extensively researched as a crucial peptide connected to the development of the characteristic amyloid fibrils in AD, the specifics of its pathophysiology are still unknown. Therefore, the main objective was to identify novel compounds that could potentially mitigate the negative effects of Aβ42. 3-[[(3S)-1,2,3,4-Tetrahydroisoquinoline-3-carbonyl]amino]propanoic acid (THICAPA) was identified as a ligand for Aβ42 and for reducing fibrillary Aβ42 aggregation. THICAPA also improved cell viability when administered to PC12 neuronal cells that were exposed to Aβ42. Additionally, this compound diminished Aβ42 toxicity in the current AD Drosophila model by rescuing the rough eye phenotype, prolonging the life span, and enhancing motor functions. Through next-generation RNA-sequencing, immune response pathways were downregulated in response to THICAPA treatment. Thus, this study suggests THICAPA as a possible disease-modifying treatment for AD. (© The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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