Alzheimer's Disease: Etiological Hypotheses and Treatment Perspectives

Falco, Anna De; Cukierman, Daphne S.; Hauser‐Davis, Rachel Ann; Rey, Nicolás A.

doi:10.5935/0100-4042.20150152

Cited by 27 publications

(28 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Recent studies have demonstrated that insulin metabolism is important in the AD signaling pathway, and there is evidence that alteration of insulin metabolism plays a role in the molecular pathogenesis of AD [45]. Patients with AD have lower levels of insulin, and when these levels are corrected, there is an improvement in cognitive processes [4], further supporting the idea that B. forficata has potential in the treatment of AD. This plant also had good anticholinesterase activity and a high antioxidant capacity and therefore could be another source of agents against AD.…”

Section: Resultsmentioning

confidence: 99%

Medicinal Plants from Northeastern Brazil against Alzheimer’s Disease

Penido

Morais

Ribeiro

et al. 2017

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Alzheimer's disease (AD) has been linked with oxidative stress, acetylcholine deficiency in the brain, and inflammatory processes. In the northeast region of Brazil, various plants are used to treat several diseases associated with these processes; then an antioxidant test was performed with those plants in a previous work and twelve species with higher antioxidant activity were selected for AChE inhibition evaluation. The phenolic compounds content was determined by Folin–Ciocalteu test and flavonoid content with AlCl3 reagent using UV-visible spectrophotometry. The antioxidant activity was assessed analyzing the inhibitory activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2-azinobis-3-ethylbenzothiazoline-6-sulfonate (ABTS) and by the β-carotene/linoleic acid system and acetylcholinesterase inhibition using qualitative and quantitative tests. The combination of better acetylcholinesterase inhibitory and antioxidant activities pointed out six species, in descending order, as the best potential sources of therapeutic agents against AD: Hancornia speciosa > Myracrodruon urundeuva > Copaifera langsdorffii > Stryphnodendron coriaceum > Psidium guajava > Mangifera indica. Besides, the phenolic compounds in the species probably contribute to these activities. However, further pharmacological studies to assess the specific applications of these plants against AD are required to confirm these results.

show abstract

Section: Resultsmentioning

confidence: 99%

Medicinal Plants from Northeastern Brazil against Alzheimer’s Disease

Penido

Morais

Ribeiro

et al. 2017

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

show abstract

“…Numa revisão de De Falco et al foram listadas seis hipóteses para as causas da DA, entre elas a hipótese da cascata amilóide, entretanto, todas elas acabam apontando para o mesmo denominador comum: a acumulação de placas amilóides no cérebro dos doentes. 3 A proteína precursora amilóide (APP, no inglês) é uma proteína membranar, a qual é atribuída a função, entre outras, de permitir a plasticidade das sinapses, um processo fundamental, tendo em vista que está diretamente relacionado com a eficiência do processo de construção da memória, do pensamento e do raciocínio. 3,4 A APP tende a sofrer clivagem pela enzima β-secretase, cujo produto de reação, um resíduo de 99 átomos de carbono, sofre clivagem pela enzima ϒ-secretase.…”

Section: Bases Moleculares Da Doença De Alzheimerunclassified

“…3 A proteína precursora amilóide (APP, no inglês) é uma proteína membranar, a qual é atribuída a função, entre outras, de permitir a plasticidade das sinapses, um processo fundamental, tendo em vista que está diretamente relacionado com a eficiência do processo de construção da memória, do pensamento e do raciocínio. 3,4 A APP tende a sofrer clivagem pela enzima β-secretase, cujo produto de reação, um resíduo de 99 átomos de carbono, sofre clivagem pela enzima ϒ-secretase. A ação desta última provoca a formação de diversos fragmentos de um peptídeo denominado β-amilóide (Aβ), no qual os dois fragmentos mais comuns são os de 40 (Aβ 1-40 ) e 42 (Aβ 1-42 ) resíduos de aminoácidos.…”

Section: Bases Moleculares Da Doença De Alzheimerunclassified

“…A ação desta última provoca a formação de diversos fragmentos de um peptídeo denominado β-amilóide (Aβ), no qual os dois fragmentos mais comuns são os de 40 (Aβ 1-40 ) e 42 (Aβ 1-42 ) resíduos de aminoácidos. 1,3 Este processo de formação de Aβ tende a se acentuar com o envelhecimento, quando o petídeo se acumula na região extracelular do cérebro do doente e forma as chamadas placas senis, causando perda neuronal e atrofia cerebral. 5 A hipótese da cascata amilóide, proposta originalmente por Hardy e Higgins em 1992, propõe que o acúmulo de Aβ no cérebro do doente é o fator principal da DA.…”

Section: Bases Moleculares Da Doença De Alzheimerunclassified

“…7 Além disso, em condições normais, essa proteína é responsável por estabilizar os microtúbulos relacionados aos axônios, mas, na presença do Aβ, esses microtúbulos acabam se desintegrando com o acúmulo da proteína, danificando as células nervosas. 1,3,7,8 O peptídeo Aβ pode adotar uma variedade de formas, dentre as quais as formas monomérica e oligomérica são as que mais servem de base para estudos, sendo atribuído à forma oligomérica o maior grau de toxicidade observado na doença, pois danifica imediatamente as sinapses quando presente no tecido cerebral. 4,9 Um estudo recente sugere que os oligômeros de Aβ (AβOs) prejudicam o funcionamento das sinapses graças a interações com proteínas essenciais para o bom funcionamento dessas.…”

Section: Bases Moleculares Da Doença De Alzheimerunclassified

See 2 more Smart Citations

Estudo Teórico De Potenciais Agentes Para O Tratamento Da Doença De Alzheimer Derivados Da 8-Hidroxiquinolina Com Substituintes Do Tipo N-Acil-Hidrazona

Silva¹,

Freitas²,

Rey³

et al. 2018

Quim. Nova

View full text Add to dashboard Cite

in the theoretical study of the coordination of three ligands derived from 8-hydroxyquinoline (8-HQ) with N-acylhydrazone: 8-hydroxyquinoline-2-carboxaldehyde isonicotinoyl hydrazone (INHHQ), 2-[(8-hydroxyquinolinyl)methylene] acetohydrazide (8-H 2 QH) and 2-[(8-hydroxyquinolinyl)methylene] hydrazinecarboxamide (8-H 2 QS); with the Zn 2+ ion. These complexes prevent interactions of the metal ions present in the brain, with the β-amyloid peptide (Aβ), avoiding the formation of aggregates that are responsible for the development of the Alzheimer's disease. The results show that the three ligands coordinate the Zn 2+ ion in a tridentate form through the O and N atoms of the 8-hydroxyquinoline center and the N of the hydrazonic group, completing the coordination sphere with two chloride ions, creating a bipyramidal structure trigonal, different from the structures of the complexes reported in the literature.

show abstract

Molecular Dynamics-Assisted Interaction of Vanadium Complex–AMPK: From Force Field Development to Biological Application for Alzheimer’s Treatment

et al. 2023

View full text Add to dashboard Cite

A large part of the world’s population is affected by Alzheimer’s disease (AD) and diabetes mellitus type 2, which cause both social and economic impacts. These two conditions are associated with one protein, AMPK. Studies have shown that vanadium complexes, such as bis(N′,N′-dimethylbiguanidato)-oxovanadium(IV), VO(metf)2·H2O, are potential agents against AD. A crucial step in drug design studies is obtaining information about the structure and interaction of these complexes with the biological targets involved in the process through molecular dynamics (MD) simulations. However, MD simulations depend on the choice of a good force field that could present reliable results. Moreover, general force fields are not efficient for describing the properties of metal complexes, and a VO(metf)2·H2O-specific force field does not yet exist; thus, the proper development of a parameter set is necessary. Furthermore, this investigation is essential and relevant given the importance for both the scientific community and the population that is affected by this neurodegenerative disease. Therefore, the present work aims to develop and validate the AMBER force field parameters for VO(metf)2·H2O since the literature lacks such information on metal complexes and investigate through classical molecular dynamics the interactions made by the complex with the protein. The proposed force field proved to be effective for describing the vanadium complex (VC), supported by different analyses and validations. Moreover, it had a great performance when compared to the general AMBER force field. Beyond that, MD findings provided an in-depth perspective of vanadium complex–protein interactions that should be taken into consideration in future studies.

show abstract

Alzheimer's Disease: Etiological Hypotheses and Treatment Perspectives

Cited by 27 publications

References 3 publications

Medicinal Plants from Northeastern Brazil against Alzheimer’s Disease

Medicinal Plants from Northeastern Brazil against Alzheimer’s Disease

Estudo Teórico De Potenciais Agentes Para O Tratamento Da Doença De Alzheimer Derivados Da 8-Hidroxiquinolina Com Substituintes Do Tipo N-Acil-Hidrazona

Molecular Dynamics-Assisted Interaction of Vanadium Complex–AMPK: From Force Field Development to Biological Application for Alzheimer’s Treatment

Contact Info

Product

Resources

About