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Volume 25
Issue 12
10.3390/ijms25126542
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Open AccessReview
by Anastasia Bougea SciProfilesScilitPreprints.orgGoogle Scholar Efthalia Angelopoulou SciProfilesScilitPreprints.orgGoogle Scholar Efthimios Vasilopoulos SciProfilesScilitPreprints.orgGoogle Scholar Philippos Gourzis SciProfilesScilitPreprints.orgGoogle Scholar Sokratis Papageorgiou SciProfilesScilitPreprints.orgGoogle ScholarAnastasia Bougea
,
Efthalia Angelopoulou
,
Efthimios Vasilopoulos
Philippos Gourzis
Sokratis Papageorgiou
1
1st Department of Neurology, “Aiginition” Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece
2
First Department of Psychiatry, “Aiginition” Hospital, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece
3
Department of Psychiatry, University of Patras, 26504 Patras, Greece
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2024, 25(12), 6542; https://doi.org/10.3390/ijms25126542 (registeringDOI)
Submission received: 29 April 2024/Revised: 6 June 2024/Accepted: 11 June 2024/Published: 13 June 2024
(This article belongs to the Special Issue Latest Review Papers in Molecular Neurobiology 2024)
Abstract
Fluoxetine, a commonly prescribed medication for depression, has been studied in Alzheimer’s disease (AD) patients for its effectiveness on cognitive symptoms. The aim of this systematic review is to investigate the therapeutic potential of fluoxetine in cognitive decline in AD, focusing on its anti-degenerative mechanisms of action and clinical implications. According to PRISMA, we searched MEDLINE, up to 1 April 2024, for animal and human studies examining the efficacy of fluoxetine with regard to the recovery of cognitive function in AD. Methodological quality was evaluated using the ARRIVE tool for animal AD studies and the Cochrane tool for clinical trials. In total, 22 studies were analyzed (19 animal AD studies and 3 clinical studies). Fluoxetine promoted neurogenesis and enhanced synaptic plasticity in preclinical models of AD, through a decrease in Aβ pathology and increase in BDNF, by activating diverse pathways (such as the DAF-16-mediated, TGF-beta1, ILK-AKT-GSK3beta, and CREB/p-CREB/BDNF). In addition, fluoxetine has anti-inflammatory properties/antioxidant effects via targeting antioxidant Nrf2/HO-1 and hindering TLR4/NLRP3 inflammasome. Only three clinical studies showed that fluoxetine ameliorated the cognitive performance of people with AD; however, several methodological issues limited the generalizability of these results. Overall, the high-quality preclinical evidence suggests that fluoxetine may have neuroprotective, antioxidant, and anti-inflammatory effects in AD animal models. While more high-quality clinical research is needed to fully understand the mechanisms underlying these effects, fluoxetine is a promising potential treatment for AD patients. If future clinical trials confirm its anti-degenerative and neuroprotective effects, fluoxetine could offer a new therapeutic approach for slowing down the progression of AD.
Keywords: fluoxetine; Alzheimer’s disease; cognitive decline; BDNF; neurogenesis
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MDPI and ACS Style
Bougea, A.; Angelopoulou, E.; Vasilopoulos, E.; Gourzis, P.; Papageorgiou, S.Emerging Therapeutic Potential of Fluoxetine on Cognitive Decline in Alzheimer’s Disease: Systematic Review. Int. J. Mol. Sci. 2024, 25, 6542.https://doi.org/10.3390/ijms25126542
AMA Style
Bougea A, Angelopoulou E, Vasilopoulos E, Gourzis P, Papageorgiou S.Emerging Therapeutic Potential of Fluoxetine on Cognitive Decline in Alzheimer’s Disease: Systematic Review. International Journal of Molecular Sciences. 2024; 25(12):6542.https://doi.org/10.3390/ijms25126542
Chicago/Turabian Style
Bougea, Anastasia, Efthalia Angelopoulou, Efthimios Vasilopoulos, Philippos Gourzis, and Sokratis Papageorgiou.2024. "Emerging Therapeutic Potential of Fluoxetine on Cognitive Decline in Alzheimer’s Disease: Systematic Review" International Journal of Molecular Sciences 25, no. 12: 6542.https://doi.org/10.3390/ijms25126542
Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.
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MDPI and ACS Style
Bougea, A.; Angelopoulou, E.; Vasilopoulos, E.; Gourzis, P.; Papageorgiou, S.Emerging Therapeutic Potential of Fluoxetine on Cognitive Decline in Alzheimer’s Disease: Systematic Review. Int. J. Mol. Sci. 2024, 25, 6542.https://doi.org/10.3390/ijms25126542
AMA Style
Bougea A, Angelopoulou E, Vasilopoulos E, Gourzis P, Papageorgiou S.Emerging Therapeutic Potential of Fluoxetine on Cognitive Decline in Alzheimer’s Disease: Systematic Review. International Journal of Molecular Sciences. 2024; 25(12):6542.https://doi.org/10.3390/ijms25126542
Chicago/Turabian Style
Bougea, Anastasia, Efthalia Angelopoulou, Efthimios Vasilopoulos, Philippos Gourzis, and Sokratis Papageorgiou.2024. "Emerging Therapeutic Potential of Fluoxetine on Cognitive Decline in Alzheimer’s Disease: Systematic Review" International Journal of Molecular Sciences 25, no. 12: 6542.https://doi.org/10.3390/ijms25126542
Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.
Int. J. Mol. Sci.,EISSN 1422-0067,Published by MDPI
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