3-[[(3S)-1,2,3,4-Tetrahydroisoquinoline-3-Carbonyl]Amino]Propanoic Acid (THICAPA) Is Protective Against Aß42-Induced Toxicity In Vitro and in an Alzheimer's Disease Drosophila.
J Gerontol A Biol Sci Med Sci
; 78(11): 1944-1952, 2023 10 28.
Article
em En
| MEDLINE
| ID: mdl-37453137
ABSTRACT
Alzheimer's disease (AD) is the most prevalent type of dementia globally. The accumulation of amyloid-beta (Aß) extracellular senile plaques in the brain is one of the hallmark mechanisms found in AD. Aß42 is the most damaging and aggressively aggregating Aß isomer produced in the brain. Although Aß42 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 Aß42. 3-[[(3S)-1,2,3,4-Tetrahydroisoquinoline-3-carbonyl]amino]propanoic acid (THICAPA) was identified as a ligand for Aß42 and for reducing fibrillary Aß42 aggregation. THICAPA also improved cell viability when administered to PC12 neuronal cells that were exposed to Aß42. Additionally, this compound diminished Aß42 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tetra-Hidroisoquinolinas
/
Doença de Alzheimer
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Gerontol A Biol Sci Med Sci
Assunto da revista:
GERIATRIA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Malásia