Brain-Derived Neurotrophic Factor Signaling in the Pathophysiology of Alzheimer’s Disease: Beneficial Effects of Flavonoids for Neuroprotection

The function of the brain-derived neurotrophic factor (BDNF) via activation through its high-affinity receptor Tropomyosin receptor kinase B (TrkB) has a pivotal role in cell differentiation, cell survival, synaptic plasticity, and both embryonic and adult neurogenesis in central nervous system neurons. A number of studies have demonstrated the possible involvement of altered expression and action of the BDNF/TrkB signaling in the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD). In this review, we introduce an essential role of the BDNF and its downstream signaling in neural function. We also review the current evidence on the deregulated the BDNF signaling in the pathophysiology of AD at gene, mRNA, and protein levels. Further, we discuss a potential usefulness of small compounds, including flavonoids, which can stimulate BDNF-related signaling as a BDNF-targeting therapy.

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The role of brain-derived neurotrophic factor and the neurotrophin receptor p75NTR in age-related brain atrophy and the transition to Alzheimer’s disease

Reviews in the Neurosciences ◽

10.1515/revneuro-2021-0111 ◽

2022 ◽

Vol 0 (0) ◽

Author(s):

Shaun Cade ◽

Xin-Fu Zhou ◽

Larisa Bobrovskaya

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Synaptic Plasticity ◽

Neurotrophic Factor ◽

Molecular Mechanisms ◽

Brain Derived Neurotrophic Factor ◽

Neurotrophin Receptor ◽

Current Evidence ◽

Synaptic Dysfunction ◽

Age Related

Abstract Alzheimer’s disease is a neurodegenerative condition that is potentially mediated by synaptic dysfunction before the onset of cognitive impairments. The disease mostly affects elderly people and there is currently no therapeutic which halts its progression. One therapeutic strategy for Alzheimer’s disease is to regenerate lost synapses by targeting mechanisms involved in synaptic plasticity. This strategy has led to promising drug candidates in clinical trials, but further progress needs to be made. An unresolved problem of Alzheimer’s disease is to identify the molecular mechanisms that render the aged brain susceptible to synaptic dysfunction. Understanding this susceptibility may identify drug targets which could halt, or even reverse, the disease’s progression. Brain derived neurotrophic factor is a neurotrophin expressed in the brain previously implicated in Alzheimer’s disease due to its involvement in synaptic plasticity. Low levels of the protein increase susceptibility to the disease and post-mortem studies consistently show reductions in its expression. A desirable therapeutic approach for Alzheimer’s disease is to stimulate the expression of brain derived neurotrophic factor and potentially regenerate lost synapses. However, synthesis and secretion of the protein are regulated by complex activity-dependent mechanisms within neurons, which makes this approach challenging. Moreover, the protein is synthesised as a precursor which exerts the opposite effect of its mature form through the neurotrophin receptor p75NTR. This review will evaluate current evidence on how age-related alterations in the synthesis, processing and signalling of brain derived neurotrophic factor may increase the risk of Alzheimer’s disease.

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A narrative review of brain-derived neurotrophic factor (BDNF) on cognitive performance in Alzheimer’s disease

Growth Factors ◽

10.1080/08977194.2020.1864347 ◽

2021 ◽

pp. 1-17

Author(s):

Noor Azila Ismail ◽

Mohammad Farris Iman Leong Abdullah ◽

Rohayu Hami ◽

Hazwani Ahmad Yusof

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Performance ◽

Neurotrophic Factor ◽

Brain Derived Neurotrophic Factor ◽

Narrative Review

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P1-031: Age-related cerebral changes of brain-derived neurotrophic factor in a model of Alzheimer's disease in APP23 transgenic mice

Alzheimer s & Dementia ◽

10.1016/j.jalz.2006.05.406 ◽

2006 ◽

Vol 2 ◽

pp. S103-S103

Author(s):

Olaf Schulte-Herbrüggen ◽

Uwe Deicke ◽

Uwe Otten ◽

Dorothee Abramowski ◽

Matthias Staufenbiel ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Transgenic Mice ◽

Neurotrophic Factor ◽

Brain Derived Neurotrophic Factor ◽

Model Of Alzheimer’S Disease ◽

Age Related

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Polymorphism at Codon 66 of the Brain-Derived Neurotrophic Factor Gene Is Not Associated with Sporadic Alzheimer’s Disease

Dementia and Geriatric Cognitive Disorders ◽

10.1159/000077736 ◽

2004 ◽

Vol 18 (1) ◽

pp. 55-58 ◽

Cited By ~ 45

Author(s):

Onofre Combarros ◽

Jon Infante ◽

Javier Llorca ◽

José Berciano

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neurotrophic Factor ◽

Brain Derived Neurotrophic Factor ◽

Sporadic Alzheimer’S Disease ◽

Factor Gene ◽

The Brain

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ANTINEURODEGENERATIVE ACTIVITY OF MICROALGAE DUNALIELLA SALINA IN RATS WITH ALZHEIMER’S DISEASE

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i1.14419 ◽

2016 ◽

Vol 10 (1) ◽

pp. 134 ◽

Cited By ~ 2

Author(s):

Farouk Kamel Elbaz ◽

Hanan F Aly ◽

Wagdy Kb Khalil ◽

Hoda F Booles ◽

Gamila H Al

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neurotrophic Factor ◽

Dunaliella Salina ◽

Brain Derived Neurotrophic Factor ◽

Male Rats ◽

Paraoxonase 1 ◽

Pon1 Activity ◽

The Brain ◽

Antioxidant Effects

ABSTRACTObjective: The present study is aimed to investigate the promising action of Dunaliella salina extract as a natural protector against Alzheimer’sdisease (AD) and reported to possess a variety of activities, including antioxidant effects due to its ability to create large amount of carotenoids.Methods: D. salina is a type of halophile green microalgae was used in the present study. 50 male rats were used in this study, where aluminumchloride was orally administered to induce AD in a dose of 100 mg/kg, daily for 6 weeks. Al-intoxicated rats treated orally daily with D. salinaethanolic extract for 6 weeks in a dose of 150 mg/kg b.wt., whereas standard anti-Alzheimer drug donepezil tartrate was administered at the doseof 10 mg/kg b.wt./day for 6 consecutive weeks. The anti-Alzheimer properties of D. salina extract were achieved through measuring the calmodulin(CaM) level, paraoxonase 1 (PON1) activity, the antiapoptotic marker (Bcl2), brain-derived neurotrophic factor (BDNF), the generation of the DNAadducts (8-hydroxy-2-deoxyguanosine [8-OHdG]/2-deoxy guanosine [2-dG]), and alteration in the expression of amyloid precursor protein, β-siteAPP-cleaving enzyme 1 (BACE1), and β-site APP-cleaving enzyme 2 (BACE2) in AD rats.Results: The current results demonstrated that supplementation of AD rats with D. salina extract-enhanced CaM level, and increased PON1 activity,upregulated Bcl2 and BDNF, decreased the levels of DNA adducts (8-OHdG/2-dG), and suppressed the alterations of the expression levels of APP,BACE1, and BACE2-m RNAs as compared with those in AD rats.Conclusion: It could be concluded that the biological activity of D. salina extract might be regulated by 9-cis b-carotene protecting the brain cells fromthe oxidative stress in AD rats.Keywords: Dunaliella salina, Calmodulin, Paraoxonase 1, Bcl2, Brain-derived neurotrophic factor, Alzheimer’s disease, DNA adduct, Amyloid precursorprotein.

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