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2.
BMJ ; 367: l6217, 2019 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-31810978

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the accumulation of amyloid ß in the form of extracellular plaques and by intracellular neurofibrillary tangles, with eventual neurodegeneration and dementia. There is currently no disease-modifying treatment though several symptomatic medications exist with modest benefit on cognition. Acetylcholinesterase inhibitors have a consistent benefit across all stages of dementia; their benefit in mild cognitive impairment and prodromal AD is unproven. Memantine has a smaller benefit on cognition overall which is limited to the moderate to severe stages, and the combination of a cholinesterase inhibitor and memantine may have additional efficacy. Evidence for the efficacy of vitamin E supplementation and medical foods is weak but might be considered in the context of cost, availability, and safety in individual patients. Apparently promising disease-modifying interventions, mostly addressing the amyloid cascade hypothesis of AD, have recently failed to demonstrate efficacy so novel approaches must be considered.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/psicologia , Peptídeos beta-Amiloides/farmacologia , Peptídeos beta-Amiloides/uso terapêutico , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/uso terapêutico , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/prevenção & controle , Preparações de Ação Retardada , Quimioterapia Combinada , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
3.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(5): 702-708, 2019 Oct 30.
Artigo em Chinês | MEDLINE | ID: mdl-31699204

RESUMO

Alzheimer's disease(AD)is a central nervous system disease characterized by progressive cognitive dysfunction and memory loss.Increasing evidences suggest that ß amyloid(Aß)plays a critical role and may be a upstream molecule in AD pathogenesis involving both genetic and environmental factors.Aß accumulation and its related inflammation are considered early events preceding neurodegeneration and neuronal loss in AD brain.However,all strategies and compounds targeting Aß deposition have failed in clinical trials,implying complexity of AD pathogenesis.This article reviews Aß hypothesis and its related mechanisms,pathophysiological process,and therapeutics of AD.


Assuntos
Doença de Alzheimer/patologia , Peptídeos beta-Amiloides , Doença de Alzheimer/prevenção & controle , Doença de Alzheimer/terapia , Encéfalo/fisiopatologia , Humanos
4.
EMBO J ; 38(23): e102345, 2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31701556

RESUMO

In Alzheimer's disease, BACE1 protease initiates the amyloidogenic processing of amyloid precursor protein (APP) that eventually results in synthesis of ß-amyloid (Aß) peptide. Aß deposition in turn causes accumulation of BACE1 in plaque-associated dystrophic neurites, thereby potentiating progressive Aß deposition once initiated. Since systemic pharmacological BACE inhibition causes adverse effects in humans, it is important to identify strategies that specifically normalize overt BACE1 activity around plaques. The microtubule-associated protein tau regulates axonal transport of proteins, and tau deletion rescues Aß-induced transport deficits in vitro. In the current study, long-term in vivo two-photon microscopy and immunohistochemistry were performed in tau-deficient APPPS1 mice. Tau deletion reduced plaque-associated axonal pathology and BACE1 accumulation without affecting physiological BACE1 expression distant from plaques. Thereby, tau deletion effectively decelerated formation of new plaques and reduced plaque compactness. The data revealed that tau reinforces Aß deposition, presumably by contributing to accumulation of BACE1 in plaque-associated dystrophies. Targeting tau-dependent mechanisms could become a suitable strategy to specifically reduce overt BACE1 activity around plaques, thereby avoiding adverse effects of systemic BACE inhibition.


Assuntos
Doença de Alzheimer/prevenção & controle , Secretases da Proteína Precursora do Amiloide/fisiologia , Ácido Aspártico Endopeptidases/antagonistas & inibidores , Regulação da Expressão Gênica , Placa Amiloide/prevenção & controle , Proteínas tau/antagonistas & inibidores , Doença de Alzheimer/etiologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Secretases da Proteína Precursora do Amiloide/genética , Secretases da Proteína Precursora do Amiloide/metabolismo , Animais , Ácido Aspártico Endopeptidases/genética , Ácido Aspártico Endopeptidases/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Placa Amiloide/etiologia , Placa Amiloide/metabolismo , Placa Amiloide/patologia
5.
J Biochem Mol Toxicol ; 33(11): e22395, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31583774

RESUMO

Raloxifene, a selective estrogen receptor modulator, displays benefits for Alzheimer's disease (AD) prevention in postmenopausal women as hormonal changes during menopause have the potential to influence AD pathogenesis, but the underlying mechanism of its neuroprotection is not entirely clear. In this study, the effects of raloxifene on amyloid-ß (Aß) amyloidogenesis were evaluated. The results demonstrated that raloxifene inhibits Aß42 aggregation and destabilizes preformed Aß42 fibrils through directly interacting with the N-terminus and middle domains of Aß42 peptides. Consequently, raloxifene not only reduces direct toxicity of Aß42 in HT22 neuronal cells, but also suppresses expressions of tumor necrosis factor-α and transforming growth factor-ß induced by Aß42 peptides, and then alleviates microglia-mediated indirect toxicity of Aß42 to HT22 neuronal cells. Our results suggested an alternative possible explanation for the neuroprotective activity of raloxifene in AD prevention.


Assuntos
Peptídeos beta-Amiloides/toxicidade , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fragmentos de Peptídeos/toxicidade , Agregados Proteicos/efeitos dos fármacos , Cloridrato de Raloxifeno/farmacologia , Doença de Alzheimer/prevenção & controle , Peptídeos beta-Amiloides/química , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Microglia/citologia , Microglia/metabolismo , Neurônios/metabolismo , Fármacos Neuroprotetores/química , Fragmentos de Peptídeos/química , Agregação Patológica de Proteínas/metabolismo , Domínios Proteicos , Cloridrato de Raloxifeno/química , Fator de Crescimento Transformador beta/genética , Fator de Necrose Tumoral alfa/genética
6.
Postgrad Med ; 131(7): 501-508, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31483196

RESUMO

Objectives: Aiginition Longitudinal Biomarker Investigation Of Neurodegeneration (ALBION) is a longitudinal ongoing study initiated in 2018 that takes place in the Cognitive Disorders Clinic of Aiginition Hospital of the National and Kapodistrian University of Athens. Its aim is to address several research questions concerning the preclinical and prodromal stage of Alzheimer's disease and explore potential markers for early detection, prediction, and primary prevention of dementia. Methods: We here present the design and the preliminary baseline characteristics of ALBION. The sample of our study consists of people aged over 50 who are concerned about their memory but are cognitively normal (CN) or have mild cognitive deficits. Each participant undergoes an extensive assessment including several demographic, medical, social, environmental, clinical, nutritional, neuropsychological determinants and lifestyle activities. Furthermore, we are collecting data from portable devices, neuroimaging techniques and biological samples (blood, stools, CSF). All participants are assessed annually for a period of 10 years. Results: In total, 47 participants have completed the initial evaluation up to date and are divided in two groups, CN individuals (N = 26) and MCI patients (N = 21), based on their cognitive status. The participants are, on average, 64 years old, 46.3% of the sample is male with an average of 12.73 years of education. MCI patients report more comorbidities and have a lower score in the MMSE test. Regarding APOE status, 2 participants are ε4 homozygotes and 10 ε4 heterozygotes. CSF analyses (Aß42, Τ-tau, P-tau) revealed no differences between the two groups. Conclusion: The ALBION study offers an opportunity to explore preclinical dementia and identify new and tailored markers, particularly relating to lifestyle. Further investigation of these populations may provide a wider profile of the changes taking place in the preclinical phase of dementia, leading to potentially effective therapeutic and preventive strategies.


Assuntos
Doença de Alzheimer/prevenção & controle , Disfunção Cognitiva/metabolismo , Prevenção Primária , Sintomas Prodrômicos , Idoso , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Apolipoproteínas E/genética , Biomarcadores , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/fisiopatologia , Diagnóstico Precoce , Eletroencefalografia , Feminino , Neuroimagem Funcional , Grécia , Humanos , Estudos Longitudinais , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/líquido cefalorraquidiano , Dados Preliminares , Proteínas tau/líquido cefalorraquidiano
8.
Psychiatriki ; 30(2): 142-155, 2019.
Artigo em Grego Moderno | MEDLINE | ID: mdl-31425142

RESUMO

Τhe rate of patients suffering from mild cognitive impairment or any type of dementia has been constantly on the rise. Considering that no effective treatment of dementia has been discovered to date and that drug use can have numerous side effects, there is an urgent need for the application of alternative, non-pharmacological interventions. To this end, the aim of this study was to investigate the effects of physical activity on the cognitive impairment of the elderly, and its use as a form of non-pharmacological intervention for the treatment of dementia. Taking a review of the relevant literature, as its data collection method, this study examined peer-reviewed papers published between 2010 and 2018 that met the criteria for their inclusion. The articles were drawn from three electronic databases (PubMed, ScienceDirect and Web of Science), and were examined with regard to the populations under consideration, research design, type of intervention programs and assessment tools applied. The vast majority of these research papers tend to support that physical activity offers significant benefits to people suffering from Alzheimer's disease or other dementias. Specifically, it helps stabilize and improve cognitive function as well as reduce and delay the onset of severe neuropsychiatric symptoms such as depression, confusion, apathy, etc. In addition, physical exercise plays an important role in improving the executive functioning of patients with dementia, increasing autonomy in their everyday activities and reducing the risk of falls. In conclusion, recent research shows physical activity to be a promising intervention for the prevention and non-pharmacological treatment of dementia in that it contributes to the improvement of patients' quality of life. However, results vary according to the particularly characteristics of the exercise under review, such as type, intensity, frequency, and duration. It is therefore important to gain both awareness and understanding of the specific factors that give physical activity its therapeutic potential leading to the development of exercise programs designed specially to treat dementia.


Assuntos
Demência/psicologia , Exercício/psicologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/prevenção & controle , Doença de Alzheimer/psicologia , Doença de Alzheimer/reabilitação , Cognição , Demência/prevenção & controle , Demência/reabilitação , Terapia por Exercício , Humanos , Qualidade de Vida
9.
J Agric Food Chem ; 67(36): 10048-10058, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31422666

RESUMO

Ginseng, the roots and rhizomes of Panax ginseng C. A. Meyer, is used not only as a herbal medicine but also as a functional food to support body functions. Ginsenoside Rg3 (GRg3) is a major bioactive component in ginseng. In this study, the beneficial effects of GRg3 on rats with Alzheimer's disease (AD) were evaluated via the behavioral experiment and antioxidant capacity. Moreover, metabolomic analysis based on UPLC-QTOF-MS/MS and apoptosis analysis was used to obtain the change between AD and GRg3-administrated rats to assess the underlying mechanisms on improving mitochondrial dysfunction. Results showed that GRg3 could prevent the cognitive impairment of AD rats by improving the mitochondrial dysfunction. The potential mechanisms were related to regulate the abnormality of energy metabolism, electron transport chain, amino acid metabolism, purine metabolism, and antiapoptosis. These findings support the exploitation of GRg3 as an effective complementary and functional food to prevent and delay AD.


Assuntos
Doença de Alzheimer/prevenção & controle , Doença de Alzheimer/psicologia , Medicamentos de Ervas Chinesas/administração & dosagem , Ginsenosídeos/administração & dosagem , Mitocôndrias/efeitos dos fármacos , Doença de Alzheimer/fisiopatologia , Aminoácidos/metabolismo , Animais , Apoptose/efeitos dos fármacos , Cognição/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Humanos , Masculino , Mitocôndrias/metabolismo , Panax/química , Ratos , Ratos Wistar
10.
Int J Mol Sci ; 20(14)2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31295812

RESUMO

Alzheimer's disease (AD), which is characterized by the presence of amyloid-ß (Aß) plaques and neurofibrillary tangles, accompanied by neurodegeneration, is the most common form of age-related neurodegenerative disease. Parkinson's disease (PD) is the second most common neurodegenerative disease after AD, and is characterized by early prominent loss of dopaminergic neurons in the substantia nigra pars compacta. As currently available treatments are not able to significantly alter the progression of these diseases, successful therapeutic and preventive interventions are strongly needed. In the course of our survey of substances from natural resources having anti-dementia and neuroprotective activity, we found nobiletin, a polymethoxylated flavone from the peel of Citrus depressa. Nobiletin improved cognitive deficits and the pathological features of AD, such as Aß pathology, hyperphosphorylation of tau, and oxidative stress, in animal models of AD. In addition, nobiletin improved motor and cognitive deficits in PD animal models. These observations suggest that nobiletin has the potential to become a novel drug for the treatment and prevention of neurodegenerative diseases such as AD and PD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Citrus/química , Flavonas/farmacologia , Flavonoides/farmacologia , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/tratamento farmacológico , Doença de Alzheimer/etiologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/prevenção & controle , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Biomarcadores , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Flavonas/química , Flavonas/uso terapêutico , Flavonoides/química , Flavonoides/uso terapêutico , Humanos , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/etiologia , Doença de Parkinson/metabolismo , Doença de Parkinson/prevenção & controle , Transdução de Sinais/efeitos dos fármacos
11.
Food Chem Toxicol ; 132: 110698, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31348966

RESUMO

The misfolding and aggregation of amyloid ß (Aß) peptide is a common histopathologic characteristic in patients with Alzheimer's disease, so is considered to play an critical role. In the present study, we examined the effect of rubrofusarin, an ingredient of Cassiae semen, on Aß aggregation and memory loss in an AD mouse model. Rubrofusarin inhibited Aß aggregation in a concentration-dependent manner. Moreover, rubrofusarin dis-aggregated preformed Aß fibrils in a concentration-dependent manner. Although aggregated Aß induced memory loss, Aß pre-incubated with rubrofusarin failed to induce memory loss. Moreover, rubrofusarin administration ameliorated Aß aggregates-induced memory loss. Finally, rubrofusarin reduced glial fibrillary acidic protein or Iba-1-positive area, markers of neuroinflammation, in the hippocampus of Aß-treated mice. These results suggest that rubrofusarin can decrease Aß fibril formation and ameliorate memory loss in the AD mouse model.


Assuntos
Doença de Alzheimer/prevenção & controle , Peptídeos beta-Amiloides/antagonistas & inibidores , Transtornos da Memória/patologia , Fragmentos de Peptídeos/antagonistas & inibidores , Pironas/farmacologia , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Modelos Animais de Doenças , Masculino , Transtornos da Memória/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Fragmentos de Peptídeos/metabolismo
12.
Int J Mol Sci ; 20(13)2019 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-31261895

RESUMO

Preventive approaches for age-related memory decline and dementia have become a high priority in the aging society because of the lack of therapeutic approaches. Recent epidemiological studies have reported that fermented dairy products can help prevent dementia. Previously, we identified tryptophan-tyrosine (WY) and tryptophan-methionine (WM) peptides as the suppressants of activation of the primary microglia and showed that WY peptide consumption suppresses inflammation in the brains of Alzheimer's disease model mice. However, the effects of the WM peptide on inflammation in the brain and Alzheimer's pathology have not been investigated. Here, we evaluated the effect of WM peptide consumption on Alzheimer's disease model (5×FAD) mice. In 5×FAD mice, intake of WM peptide suppressed the production of inflammatory cytokines, activation of microglia, and infiltration of activated microglia around ß amyloid (Aß) depositions. WM peptide intake reduced Aß deposition in the cortex and hippocampus and then improved the object recognition memory. Taken together with previous reports, the current findings indicate that ingestion of tryptophan-related peptides or food material rich in tryptophan-related peptides, thereby regulating microglial activity, represents a potential preventive approach for cognitive decline and dementia related to inflammation.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Dipeptídeos/farmacologia , Doença de Alzheimer/prevenção & controle , Peptídeos beta-Amiloides/metabolismo , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Citocinas/metabolismo , Suplementos Nutricionais , Dipeptídeos/administração & dosagem , Dipeptídeos/química , Dipeptídeos/uso terapêutico , Feminino , Metionina/química , Camundongos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Proteínas do Leite/química , Triptofano/química
13.
Int J Mol Sci ; 20(11)2019 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-31181669

RESUMO

The risk of Alzheimer's disease (AD) increases with nonmodifiable conditions including age and lack of effective efficacious pharmacotherapy. During the past decades, the non-pharmacotherapy mode of treatment of dietary modification received extensive attention in AD research. In order to reduce the AD pathology and cognitive decline, various dietary patterns have been attempted including caloric restriction (CR), dietary approaches to stop hypertension (DASH), ketogenic diets (KD), Mediterranean diet (MedDi) and Mediterranean-DASH diet Intervention for Neurological Delay (MIND) diet. Higher adherence to the MedDi diet was associated with decreases in cardiovascular and neurological disorders including AD and related cognitive decline. However, another emerging healthy dietary pattern MIND diet has also been associated with slower rates of cognitive decline and significant reduction of AD rate. Olive serves as one of the building block components of MedDi and MIND diets and the exerted potential health beneficial might be suggested due to the presence of its bioactive constituents such as oleic acids and phenolic compounds (biophenols). A few trials using medical food showed an optimal result in presymptomatic or early stages of AD. The review supports the notion that MedDi and MIND diets display potential for maintaining the cognitive function as nonpharmacological agents against AD pathology and proposed preventative mechanism through the presence of olive biophenols and presents the gaps along with the future directions.


Assuntos
Doença de Alzheimer/dietoterapia , Dieta Mediterrânea , Azeite de Oliva/uso terapêutico , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/prevenção & controle , Cognição/efeitos dos fármacos , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Humanos , Azeite de Oliva/farmacologia
14.
Proc Jpn Acad Ser B Phys Biol Sci ; 95(6): 290-294, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31189781

RESUMO

Alzheimer's disease (AD) is one of the major causes of chronic and progressive cognitive decline, with the pathological hallmarks of senile plaques and neurofibrillary tangles. Amyloid ß peptide (Aß) is the main component of senile plaques, and the pathological load of Aß in the brain has been shown to be a marker of the severity of AD. To prevent the accumulation of plaques, novel and safer plant-based vaccine strategies have been suggested. In this review, we summarize the results of plant vaccines against Aß.


Assuntos
Doença de Alzheimer/imunologia , Biotecnologia/métodos , Plantas , Vacinas/imunologia , Doença de Alzheimer/prevenção & controle , Animais , Humanos , Plantas/genética , Vacinas/genética
15.
J Agric Food Chem ; 67(27): 7684-7693, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31203623

RESUMO

This study investigated the alleviative effect of caffeic acid (CA) on Alzheimer's disease (AD) pathogenesis and associated mechanisms in high-fat (HF) diet-induced hyperinsulinemic rats. The results of a Morris water maze indicated that, by administrating CA (30 mg/kg b.w./day) for 30 weeks, the memory and learning impairments in HF-induced hyperinsulinemic rats were significantly ameliorated. CA also enhanced superoxide dismutase and glutathione free radical scavenger activity in hyperinsulinemic rats. The Western blot data further confirmed that protein expressions of phosphorylated-glycogen synthase kinase 3ß (GSK3ß) were significantly increased, whereas the expression of phosphorylated-tau protein decreased in the hippocampus of rats administered with CA in comparison with the HF group. Moreover, the expression of amyloid precursor protein (APP) and ß-site APP cleaving enzyme were attenuated, subsequently lowering the level of ß-amyloid 1-42 (Aß 1-42) in the hippocampus of CA-treated hyperinsulinemic rats. CA also significantly increased the expression of synaptic proteins in HF rats.


Assuntos
Doença de Alzheimer/prevenção & controle , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Ácidos Cafeicos/administração & dosagem , Insulina/metabolismo , Plasticidade Neuronal/efeitos dos fármacos , Doença de Alzheimer/metabolismo , Animais , Antioxidantes/química , Córtex Cerebral/química , Córtex Cerebral/enzimologia , Córtex Cerebral/metabolismo , Dieta Hiperlipídica , Modelos Animais de Doenças , Glutationa/metabolismo , Glicogênio Sintase Quinase 3 beta/análise , Glicogênio Sintase Quinase 3 beta/metabolismo , Hipocampo/química , Hipocampo/enzimologia , Hipocampo/metabolismo , Hiperinsulinismo/etiologia , Hiperinsulinismo/metabolismo , Masculino , Fosforilação , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Proteínas tau/análise , Proteínas tau/metabolismo
16.
Molecules ; 24(12)2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-31226738

RESUMO

Alzheimer's disease (AD) is the most common type of dementia and is the leading cause of disability in elderly people worldwide. Current pharmacological therapies do not cure the disease, and for this reason, some pharmacotherapy studies have investigated preventive treatments focused on modifiable nutritional factors such as diet. Quercetin (Qc) is a flavonoid found in fruits and vegetables that has several biological properties. In this study, we evaluated the effect of chronic oral quercetin administration (100 mg/kg) on neurodegeneration markers and cognitive and emotional deficits in a triple transgenic Alzheimer's disease (3xTg-AD) mouse model using histological and behavioral analyses. Our results suggest that long-term (12 months) oral preventive treatment with quercetin has significant effects on ß-amyloidosis reduction and tends to decrease tauopathy in the hippocampus and amygdala. These decreases positively affected the cognitive functional recovery (without modifying the emotional skills) of 3xTg-AD mice. These findings suggest that preventive and chronic administration of Qc might help to delay the development of histopathological hallmarks and cognitive function deficits in AD.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Transtornos Cognitivos/tratamento farmacológico , Quercetina/farmacologia , Proteínas tau/genética , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Doença de Alzheimer/prevenção & controle , Peptídeos beta-Amiloides/genética , Precursor de Proteína beta-Amiloide/genética , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Transtornos Cognitivos/genética , Transtornos Cognitivos/patologia , Transtornos Cognitivos/prevenção & controle , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Humanos , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Transgênicos
17.
Life Sci ; 229: 21-35, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31063734

RESUMO

BACKGROUND: Alzheimer's disease is a neurodegenerative disorder characterized by a progressive decline of cognitive abilities as well as bone loss. Physical and mental activities maintain cognitive functions as well as increase bone mass by inhibiting bone resorption. VIN and CoQ10 are neuroprotective drugs that possess anti-inflammatory and antioxidant properties. AIMS: To study the effect of PH&M on enhancing the neuroprotective role of VIN and CoQ10 combination during induction of AD model in rats besides their role against bone mass loss associated with AD model. MAIN METHODS: Six groups of rats were received saline, AlCl3, and PH&M daily either alone or with a combination of VIN and CoQ10 for 4 weeks. Various biochemical analyses were performed to evaluate the extent of brain damage such as ACHE, ß-secretase, chitinase, Aß, tau protein, and monoamines besides the inflammatory and antioxidant parameters. Serum levels of minerals as well as 25-OHD, PTH, RANKL, and OPG levels were measured to detect the extent of bone impairment. Also, histopathological changes were evaluated in different brain regions and hind paw. KEY FINDINGS: VIN and CoQ10 combination together with PH&M significantly attenuated the neurodegeneration induced by AlCl3 administration through the improvement of AD markers in brain tissue as well as oxidant and inflammatory markers. Bone resorption markers, serum minerals, and PTH levels were also normalized too. SIGNIFICANCE: Neuroprotective drugs together with PH&M have a more protective effect against AD and bone loss rather than PH&M alone.


Assuntos
Doença de Alzheimer/prevenção & controle , Remodelação Óssea/fisiologia , Cognição , Fármacos Neuroprotetores/farmacologia , Natação , Ubiquinona/análogos & derivados , Alcaloides de Vinca/farmacologia , Doença de Alzheimer/metabolismo , Animais , Comportamento Animal , Remodelação Óssea/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/fisiologia , Terapia Combinada , Masculino , Ratos , Ratos Sprague-Dawley , Ubiquinona/farmacologia , Vitaminas/farmacologia
18.
Nutrients ; 11(5)2019 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-31137655

RESUMO

Dementia has become a major issue that requires urgent measures. The prevention of dementia may be influenced by dietary factors. We focused on green tea and performed a systematic review of observational studies that examined the association between green tea intake and dementia, Alzheimer's disease, mild cognitive impairment, or cognitive impairment. We searched for articles registered up to 23 August 2018, in the PubMed database and then for references of original articles or reviews that examined tea and cognition. Subsequently, the extracted articles were examined regarding whether they included original data assessing an association of green tea intake and dementia, Alzheimer's disease, mild cognitive impairment, or cognitive impairment. Finally, we included three cohort studies and five cross-sectional studies. One cohort study and three cross-sectional studies supported the positive effects of green tea intake. One cohort study and one cross-sectional study reported partial positive effects. The remaining one cohort study and one cross-sectional study showed no significant association of green tea intake. These results seem to support the hypothesis that green tea intake might reduce the risk for dementia, Alzheimer's disease, mild cognitive impairment, or cognitive impairment. Further results from well-designed and well-conducted cohort studies are required to derive robust evidence.


Assuntos
Doença de Alzheimer/prevenção & controle , Camellia sinensis , Cognição , Envelhecimento Cognitivo/psicologia , Disfunção Cognitiva/prevenção & controle , Chá , Adulto , Fatores Etários , Idoso , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/psicologia , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Fatores de Proteção , Medição de Risco , Fatores de Risco
19.
Int J Mol Sci ; 20(8)2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-31014012

RESUMO

Alzheimer's disease (AD) is a progressive neurodegenerative disorder more prevalent among the elderly population. AD is characterised clinically by a progressive decline in cognitive functions and pathologically by the presence of neurofibrillary tangles (NFTs), deposition of beta-amyloid (Aß) plaque and synaptic dysfunction in the brain. Centella asiatica (CA) is a valuable herb being used widely in African, Ayurvedic, and Chinese traditional medicine to reverse cognitive impairment and to enhance cognitive functions. This study aimed to evaluate the effectiveness of CA in preventing d-galactose/aluminium chloride (d-gal/AlCl3) induced AD-like pathologies and the underlying mechanisms of action were further investigated for the first time. Results showed that co-administration of CA to d-gal/AlCl3 induced AD-like rat models significantly increased the levels of protein phosphatase 2 (PP2A) and decreased the levels of glycogen synthase kinase-3 beta (GSK-3ß). It was further observed that, CA increased the expression of mRNA of Bcl-2, while there was minimal effect on the expression of caspase 3 mRNA. The results also showed that, CA prevented morphological aberrations in the connus ammonis 3 (CA 3) sub-region of the rat's hippocampus. The results clearly demonstrated for the first time that CA could alleviate d-gal/AlCl3 induced AD-like pathologies in rats via inhibition of hyperphosphorylated tau (P-tau) bio-synthetic proteins, anti-apoptosis and maintenance of cytoarchitecture.


Assuntos
Doença de Alzheimer/prevenção & controle , Centella/química , Hipocampo/metabolismo , Transdução de Sinais/efeitos dos fármacos , Triterpenos/farmacologia , Cloreto de Alumínio/química , Cloreto de Alumínio/toxicidade , Doença de Alzheimer/etiologia , Doença de Alzheimer/veterinária , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Centella/metabolismo , Galactose/química , Galactose/toxicidade , Glicogênio Sintase Quinase 3 beta/metabolismo , Hipocampo/efeitos dos fármacos , Masculino , Proteína Fosfatase 2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Wistar , Triterpenos/química , Triterpenos/uso terapêutico
20.
Curr Med Sci ; 39(2): 196-203, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31016510

RESUMO

With the intensification of the aging process of the world, Alzheimer's disease (AD), which is the main type of senile dementia, has become a primary problem in the present society. Lots of strategies have been used to prevent and treat AD in animal models and clinical trials, but most of them ended in failure. Panax notoginseng saponins (PNS) contain a variety of monomer compositions which have been separated and identified. Among of the monomer compositions, notoginseng saponin Rg1 (Rg1) accounts for 20% of the cultivation of panax notoginseng roots. And now PNS have been reported to be widely used to treat cardio-cerebrovascular diseases and have neuroprotective effects to restrain the ß-amyloid peptide (Aß)25-35-mediated apoptosis. Moreover, it is reported that PNS could accelerate the growth of nerve cells, increase the length of axons and promote synaptic plasticity. Whether Rg1 can ameliorate the cognitive impairment and the underlying mechanism has not been elucidated. To study the preventive effect of Rg1 on cognitive impairment and the possible mechanism, we established the cognitive impairment model in rats through Aß1-42 (2.6 µg/µL, 5 µL) injection and then treated the rats with Rg1 (25, 50 and 100 mg/kg) administered intragastrically for 4 weeks. We observed that Aß1-42 could induce spatial learning and memory deficits in rats. Simultaneously, Aß1-42 injection also resulted in the reduced neuron number in cornuammonis 1 (CA1) and dentate gyrus (DG) of hippocampus, as well as the increased level of hyperphosphorylated ß-amyloid precursor protein (APP) at Thr668 site with up-regulation of ß-APP cleaving enzyme 1 (BACE1) and presenilin 1 (PS1) and down-regulation of a disintegrin and metalloprotease domain-containing protein 10 (ADAM10) and insulin-degrading enzyme (IDE). Administration of Rg1 effectively rescued the cognitive impairment and neuronal loss, and inhibited the ß-secretase processing of APP through reducing APP-Thr668 phosphorylation and BACE1/PS1 expression, and increasing the expression of ADAM10 and IDE. We concluded that Rg1 might have neuroprotective effects and could promote learning and memory ability, which might be a viable candidate in AD therapy probably through reducing the generation of Aß and increasing the degradation of Aß.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Disfunção Cognitiva/prevenção & controle , Panax notoginseng/química , Fragmentos de Peptídeos/metabolismo , Saponinas/farmacologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/prevenção & controle , Secretases da Proteína Precursora do Amiloide/metabolismo , Animais , Disfunção Cognitiva/metabolismo , Giro Denteado/efeitos dos fármacos , Giro Denteado/metabolismo , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Aprendizagem/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Transtornos da Memória/metabolismo , Transtornos da Memória/prevenção & controle , Fármacos Neuroprotetores/farmacologia , Presenilina-1/metabolismo , Ratos , Ratos Sprague-Dawley
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