RT Journal Article
T1 Exploring the Multi-Target Performance of Mitochondriotropic Antioxidants against the Pivotal Alzheimer’s Disease Pathophysiological Hallmarks
A1 Benfeito, Sofia
A1 Fernandes, Carlos
A1 Vilar, Santiago
A1 Remião, Fernando
A1 Uriarte Villares, Eugenio
A1 Borges, Fernanda
K1 Alzheimer disease
K1 Mitochondriotropic antioxidants
K1 Cholinesterase inhibitors
K1 Oxidative stress
K1 β-amyloid
K1 Iron accumulation
K1 Excitotoxicity
AB Alzheimer disease (AD) is the most common neurodegenerative disease featuring progressive and degenerative neurological impairments resulting in memory loss and cognitive decline. The specific mechanisms underlying AD are still poorly understood, but it is suggested that a deficiency in the brain neurotransmitter acetylcholine, the deposition of insoluble aggregates of fibrillar β-amyloid 1–42 (Aβ42), and iron and glutamate accumulation play an important role in the disease progress. Despite the existence of approved cholinergic drugs, none of them demonstrated effectiveness in modifying disease progression. Accordingly, the development of new chemical entities acting on more than one target is attracting progressively more attention as they can tackle intricate network targets and modulate their effects. Within this endeavor, a series of mitochondriotropic antioxidants inspired on hydroxycinnamic (HCA’s) scaffold were synthesized, screened toward cholinesterases and evaluated as neuroprotectors in a differentiated human SH-SY5Y cell line. From the series, compounds 7 and 11 with a 10-carbon chain can be viewed as multi-target leads for the treatment of AD, as they act as dual and bifunctional cholinesterase inhibitors and prevent the neuronal damage caused by diverse aggressors related to protein misfolding and aggregation, iron accumulation and excitotoxicity
PB MDPI
YR 2020
FD 2020
LK http://hdl.handle.net/10347/23522
UL http://hdl.handle.net/10347/23522
LA eng
NO Benfeito, S.; Fernandes, C.; Vilar, S.; Remião, F.; Uriarte, E.; Borges, F. Exploring the Multi-Target Performance of Mitochondriotropic Antioxidants against the Pivotal Alzheimer’s Disease Pathophysiological Hallmarks. Molecules 2020, 25, 276
NO This work was funded by FEDER funds through the Operational Programme Competitiveness Factors-COMPETE and national funds by FCT-Foundation for Science and Technology under research grants (UID/QUI/00081, NORTE-01-0145-FEDER-000028, PTDC/DTP-FTO/2433/2014, PTDC/BIA-MOL/28607/2017, POCI-01-0145-FEDER-028607). S. Benfeito and C. Fernandes grants are supported by FCT, POPH and QREN. The authors also thank the COST action CA15135 for support
DS Minerva
RD 28 abr 2026