10.3389/fphar.2019.00658.s003
Fabiana Morroni
Fabiana
Morroni
Giulia Sita
Giulia
Sita
Agnese Graziosi
Agnese
Graziosi
Gloria Ravegnini
Gloria
Ravegnini
Raffaella Molteni
Raffaella
Molteni
Maria Serena Paladini
Maria Serena
Paladini
Kris Simone Tranches Dias
Kris Simone Tranches
Dias
Ariele Faria dos Santos
Ariele Faria dos
Santos
Claudio Viegas
Claudio
Viegas
Ihosvany Camps
Ihosvany
Camps
Letizia Pruccoli
Letizia
Pruccoli
Andrea Tarozzi
Andrea
Tarozzi
Patrizia Hrelia
Patrizia
Hrelia
DataSheet_3_PQM130, a Novel Feruloyl–Donepezil Hybrid Compound, Effectively Ameliorates the Cognitive Impairments and Pathology in a Mouse Model of Alzheimer’s Disease.pdf
Frontiers
2019
Alzheimer’s disease
amyloid-β oligomers
oxidative stress
apoptosis
neuroprotection
multitarget ligand
drug discovery
feruloyl-donepezil hybrid
2019-06-12 04:37:47
Dataset
https://frontiersin.figshare.com/articles/dataset/DataSheet_3_PQM130_a_Novel_Feruloyl_Donepezil_Hybrid_Compound_Effectively_Ameliorates_the_Cognitive_Impairments_and_Pathology_in_a_Mouse_Model_of_Alzheimer_s_Disease_pdf/8260652
<p>Alzheimer’s disease (AD) is the most frequent type of dementia in older people. The complex nature of AD calls for the development of multitarget agents addressing key pathogenic processes. Donepezil, an acetylcholinesterase inhibitor, is a first-line acetylcholinesterase inhibitor used for the treatment of AD. Although several studies have demonstrated the symptomatic efficacy of donepezil treatment in AD patients, the possible effects of donepezil on the AD process are not yet known. In this study, a novel feruloyl–donepezil hybrid compound (PQM130) was synthesized and evaluated as a multitarget drug candidate against the neurotoxicity induced by Aβ<sub>1-42</sub> oligomer (AβO) injection in mice. Interestingly, PQM130 had already shown anti-inflammatory activity in different in vivo models and neuroprotective activity in human neuronal cells. The intracerebroventricular (i.c.v.) injection of AβO in mice caused the increase of memory impairment, oxidative stress, neurodegeneration, and neuroinflammation. Instead, PQM130 (0.5–1 mg/kg) treatment after the i.c.v. AβO injection reduced oxidative damage and neuroinflammation and induced cell survival and protein synthesis through the modulation of glycogen synthase kinase 3β (GSK3β) and extracellular signal–regulated kinases (ERK1/2). Moreover, PQM130 increased brain plasticity and protected mice against the decline in spatial cognition. Even more interesting is that PQM130 modulated different pathways compared to donepezil, and it is much more effective in counteracting AβO damage. Therefore, our findings highlighted that PQM130 is a potent multi-functional agent against AD and could act as a promising neuroprotective compound for anti-AD drug development.</p>