Base de dados : MEDLINE
Pesquisa : D12.776.049.407.249 [Categoria DeCS]
Referências encontradas : 10568 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 1057 ir para página                         

  1 / 10568 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29348617
[Au] Autor:Miranda AM; Lasiecka ZM; Xu Y; Neufeld J; Shahriar S; Simoes S; Chan RB; Oliveira TG; Small SA; Di Paolo G
[Ad] Endereço:Department of Pathology and Cell Biology, Columbia University Medical Center, New York, NY, 10032, USA.
[Ti] Título:Neuronal lysosomal dysfunction releases exosomes harboring APP C-terminal fragments and unique lipid signatures.
[So] Source:Nat Commun;9(1):291, 2018 01 18.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Defects in endolysosomal and autophagic functions are increasingly viewed as key pathological features of neurodegenerative disorders. A master regulator of these functions is phosphatidylinositol-3-phosphate (PI3P), a phospholipid synthesized primarily by class III PI 3-kinase Vps34. Here we report that disruption of neuronal Vps34 function in vitro and in vivo impairs autophagy, lysosomal degradation as well as lipid metabolism, causing endolysosomal membrane damage. PI3P deficiency also promotes secretion of unique exosomes enriched for undigested lysosomal substrates, including amyloid precursor protein C-terminal fragments (APP-CTFs), specific sphingolipids, and the phospholipid bis(monoacylglycero)phosphate (BMP), which normally resides in the internal vesicles of endolysosomes. Secretion of these exosomes requires neutral sphingomyelinase 2 and sphingolipid synthesis. Our results reveal a homeostatic response counteracting lysosomal dysfunction via secretion of atypical exosomes eliminating lysosomal waste and define exosomal APP-CTFs and BMP as candidate biomarkers for endolysosomal dysfunction associated with neurodegenerative disorders.
[Mh] Termos MeSH primário: Precursor de Proteína beta-Amiloide/metabolismo
Exossomos/metabolismo
Lipídeos/análise
Lisossomos/metabolismo
Neurônios/metabolismo
[Mh] Termos MeSH secundário: Precursor de Proteína beta-Amiloide/química
Animais
Autofagia/genética
Biomarcadores/metabolismo
Linhagem Celular Tumoral
Classe III de Fosfatidilinositol 3-Quinases/genética
Classe III de Fosfatidilinositol 3-Quinases/metabolismo
Células HEK293
Seres Humanos
Lisofosfolipídeos/metabolismo
Camundongos Endogâmicos C57BL
Camundongos Knockout
Monoglicerídeos/metabolismo
Doenças Neurodegenerativas/diagnóstico
Doenças Neurodegenerativas/metabolismo
Fragmentos de Peptídeos/metabolismo
Fosfatos de Fosfatidilinositol/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amyloid beta-Protein Precursor); 0 (Biomarkers); 0 (Lipids); 0 (Lysophospholipids); 0 (Monoglycerides); 0 (Peptide Fragments); 0 (Phosphatidylinositol Phosphates); 0 (bis(monoacylglyceryl)phosphate); 0 (phosphatidylinositol 3-phosphate); EC 2.7.1.137 (Class III Phosphatidylinositol 3-Kinases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180120
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02533-w


  2 / 10568 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28449688
[Au] Autor:Li ZY; Chung YH; Shin EJ; Dang DK; Jeong JH; Ko SK; Nah SY; Baik TG; Jhoo JH; Ong WY; Nabeshima T; Kim HC
[Ad] Endereço:Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, 24341, Republic of Korea.
[Ti] Título:YY-1224, a terpene trilactone-strengthened Ginkgo biloba, attenuates neurodegenerative changes induced by ß-amyloid (1-42) or double transgenic overexpression of APP and PS1 via inhibition of cyclooxygenase-2.
[So] Source:J Neuroinflammation;14(1):94, 2017 Apr 27.
[Is] ISSN:1742-2094
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Ginkgo biloba has been reported to possess free radical-scavenging antioxidant activity and anti-inflammatory properties. In our pilot study, YY-1224, a terpene trilactone-strengthened extract of G. biloba, showed anti-inflammatory, neurotrophic, and antioxidant effects. RESULTS: We investigated the pharmacological potential of YY-1224 in ß-amyloid (Aß) (1-42)-induced memory impairment using cyclooxygenase-2 (COX-2) knockout (-/-) and APPswe/PS1dE9 transgenic (APP/PS1 Tg) mice. Repeated treatment with YY-1224 significantly attenuated Aß (1-42)-induced memory impairment in COX-2 (+/+) mice, but not in COX-2 (-/-) mice. YY-1224 significantly attenuated Aß (1-42)-induced upregulation of platelet-activating factor (PAF) receptor gene expression, reactive oxygen species, and pro-inflammatory factors. In addition, YY-1224 significantly inhibited Aß (1-42)-induced downregulation of PAF-acetylhydrolase-1 (PAF-AH-1) and peroxisome proliferator-activated receptor γ (PPARγ) gene expression. These changes were more pronounced in COX-2 (+/+) mice than in COX-2 (-/-) mice. YY-1224 significantly attenuated learning impairment, Aß deposition, and pro-inflammatory microglial activation in APP/PS1 Tg mice, whereas it significantly enhanced PAF-AH and PPARγ expression. A preferential COX-2 inhibitor, meloxicam, did not affect the pharmacological activity by YY-1224, suggesting that the COX-2 gene is a critical mediator of the neuroprotective effects of YY-1224. The protective activity of YY-1224 appeared to be more efficacious than a standard G. biloba extract (Gb) against Aß insult. CONCLUSIONS: Our results suggest that the protective effects of YY-1224 against Aß toxicity may be associated with its PAF antagonistic- and PPARγ agonistic-potential as well as inhibition of the Aß-mediated pro-inflammatory switch of microglia phenotypes through suppression of COX-2 expression.
[Mh] Termos MeSH primário: Peptídeos beta-Amiloides/toxicidade
Ciclo-Oxigenase 2/metabolismo
Ginkgo biloba
Doenças Neurodegenerativas/metabolismo
Fragmentos de Peptídeos/toxicidade
Extratos Vegetais/uso terapêutico
[Mh] Termos MeSH secundário: Doença de Alzheimer/tratamento farmacológico
Doença de Alzheimer/genética
Doença de Alzheimer/metabolismo
Precursor de Proteína beta-Amiloide/biossíntese
Precursor de Proteína beta-Amiloide/genética
Animais
Expressão Gênica
Lactonas/isolamento & purificação
Lactonas/uso terapêutico
Camundongos
Camundongos Knockout
Camundongos Transgênicos
Doenças Neurodegenerativas/genética
Doenças Neurodegenerativas/prevenção & controle
Extratos Vegetais/isolamento & purificação
Extratos Vegetais/farmacologia
Presenilina-1/biossíntese
Presenilina-1/genética
Espécies Reativas de Oxigênio/antagonistas & inibidores
Espécies Reativas de Oxigênio/metabolismo
Terpenos/isolamento & purificação
Terpenos/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amyloid beta-Peptides); 0 (Amyloid beta-Protein Precursor); 0 (Lactones); 0 (Peptide Fragments); 0 (Plant Extracts); 0 (Presenilin-1); 0 (Reactive Oxygen Species); 0 (Terpenes); 0 (amyloid beta-protein (1-42)); 0 (trilactone); EC 1.14.99.1 (Cyclooxygenase 2)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1186/s12974-017-0866-x


  3 / 10568 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
[PMID]:28930532
[Au] Autor:Ahmad Rather M; Justin Thenmozhi A; Manivasagam T; Dhivya Bharathi M; Essa MM; Guillemin GJ
[Ad] Endereço:Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar, Tamil Nadu 608002, India.
[Ti] Título:Neuroprotective role of Asiatic acid in aluminium chloride induced rat model of Alzheimer's disease.
[So] Source:Front Biosci (Schol Ed);10:262-275, 2018 01 01.
[Is] ISSN:1945-0524
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Alzheimer's disease (AD) is the most common form of dementia, characterized by memory loss, cognitive impairment and personality disorders accompanied by diffuse structural abnormalities in the brain of elderly people. The current investigation explored the neuroprotective potential of asiatic acid (AA), a natural triterpene of on aluminium chloride (AlCl ) induced rat model of AD. Oral administration of AlCl (100 mg/kg b.w.) for 42 days significantly elevated the levels of Al, activity of acetyl cholinesterase and expressions of amyloid precursor protein, amyloid beta , beta and gamma secretases, glial fibrillary acidic protein, ionized calcium binding adaptor molecule 1, interleukins -1ß, 6, 4, 2, tumor necrosis factor alpha, inducible nitric oxide synthase, nuclear factor- k beta and cyclooxygenase-2 in the hippocampus and cortex  compared to the control group. Our observations suggested that AA treatment mitigated AlCl induced AD associated pathologies, which might be due to its multiple pharmacological actions. Further studies are necessary in order to explore the link between AlCl -mediated oxidative stress and associated apoptosis to establish its neuroprotective role in AD.
[Mh] Termos MeSH primário: Doença de Alzheimer/tratamento farmacológico
Fármacos Neuroprotetores/farmacologia
Triterpenos Pentacíclicos/farmacologia
[Mh] Termos MeSH secundário: Compostos de Alumínio
Doença de Alzheimer/induzido quimicamente
Doença de Alzheimer/metabolismo
Doença de Alzheimer/patologia
Amiloide/metabolismo
Secretases da Proteína Precursora do Amiloide/metabolismo
Peptídeos beta-Amiloides/metabolismo
Precursor de Proteína beta-Amiloide/metabolismo
Animais
Apoptose/efeitos dos fármacos
Cloretos
Modelos Animais de Doenças
Masculino
Estresse Oxidativo/efeitos dos fármacos
Distribuição Aleatória
Ratos
Ratos Wistar
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aluminum Compounds); 0 (Amyloid); 0 (Amyloid beta-Peptides); 0 (Amyloid beta-Protein Precursor); 0 (Chlorides); 0 (Neuroprotective Agents); 0 (Pentacyclic Triterpenes); 3CYT62D3GA (aluminum chloride); 9PA5A687X5 (asiatic acid); EC 3.4.- (Amyloid Precursor Protein Secretases)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170921
[St] Status:MEDLINE


  4 / 10568 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29320530
[Au] Autor:Plummer SL; Corrigan F; Thornton E; Woenig JA; Vink R; Cappai R; Van Den Heuvel C
[Ad] Endereço:Translational Neuropathology Laboratory, The University of Adelaide, Adelaide, South Australia, Australia.
[Ti] Título:The amyloid precursor protein derivative, APP96-110, is efficacious following intravenous administration after traumatic brain injury.
[So] Source:PLoS One;13(1):e0190449, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Following traumatic brain injury (TBI) neurological damage is ongoing through a complex cascade of primary and secondary injury events in the ensuing minutes, days and weeks. The delayed nature of secondary injury provides a valuable window of opportunity to limit the consequences with a timely treatment. Recently, the amyloid precursor protein (APP) and its derivative APP96-110 have shown encouraging neuroprotective activity following TBI following an intracerebroventricular administration. Nevertheless, its broader clinical utility would be enhanced by an intravenous (IV) administration. This study assessed the efficacy of IV APP96-110, where a dose-response for a single dose of 0.005mg/kg- 0.5mg/kg APP96-110 at either 30 minutes or 5 hours following moderate-severe diffuse impact-acceleration injury was performed. Male Sprague-Dawley rats were assessed daily for 3 or 7 days on the rotarod to examine motor outcome, with a separate cohort of animals utilised for immunohistochemistry analysis 3 days post-TBI to assess axonal injury and neuroinflammation. Animals treated with 0.05mg/kg or 0.5mg/kg APP96-110 after 30 minutes demonstrated significant improvements in motor outcome. This was accompanied by a reduction in axonal injury and neuroinflammation in the corpus callosum at 3 days post-TBI, whereas 0.005mg/kg had no effect. In contrast, treatment with 0.005m/kg or 0.5mg/kg APP96-110 at 5 hours post-TBI demonstrated significant improvements in motor outcome over 3 days, which was accompanied by a reduction in axonal injury in the corpus callosum. This demonstrates that APP96-110 remains efficacious for up to 5 hours post-TBI when administered IV, and supports its development as a novel therapeutic compound following TBI.
[Mh] Termos MeSH primário: Precursor de Proteína beta-Amiloide/administração & dosagem
Lesões Encefálicas Traumáticas/tratamento farmacológico
[Mh] Termos MeSH secundário: Administração Intravenosa
Animais
Masculino
Ratos
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amyloid beta-Protein Precursor)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180206
[Lr] Data última revisão:
180206
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180111
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190449


  5 / 10568 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27777419
[Au] Autor:Kaur G; Pawlik M; Gandy SE; Ehrlich ME; Smiley JF; Levy E
[Ad] Endereço:Center of Dementia Research, Nathan S. Kline Institute, Orangeburg, NY, USA.
[Ti] Título:Lysosomal dysfunction in the brain of a mouse model with intraneuronal accumulation of carboxyl terminal fragments of the amyloid precursor protein.
[So] Source:Mol Psychiatry;22(7):981-989, 2017 Jul.
[Is] ISSN:1476-5578
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Recent data suggest that intraneuronal accumulation of metabolites of the amyloid-ß-precursor protein (APP) is neurotoxic. We observed that transgenic mice overexpressing in neurons a human APP gene harboring the APP (Dutch) mutation have intraneuronal lysosomal accumulation of APP carboxylterminal fragments (APP-CTFs) and oligomeric amyloid ß (oAß) but no histological evidence of amyloid deposition. Morphometric quantification using the lysosomal marker protein 2 (LAMP-2) immunolabeling showed higher neuronal lysosomal counts in brain of 12-months-old APP as compared with age-matched non-transgenic littermates, and western blots showed increased lysosomal proteins including LAMP-2, cathepsin D and LC3. At 24 months of age, these mice also exhibited an accumulation of α-synuclein in the brain, along with increased conversion of LC3-I to LC3-II, an autophagosomal/autolysosomal marker. In addition to lysosomal changes at 12 months of age, these mice developed cholinergic neuronal loss in the basal forebrain, GABAergic neuronal loss in the cortex, hippocampus and basal forebrain and gliosis and microgliosis in the hippocampus. These findings suggest a role for the intraneuronal accumulation of oAß and APP-CTFs and resultant lysosomal pathology at early stages of Alzheimer's disease-related pathology.
[Mh] Termos MeSH primário: Peptídeos beta-Amiloides/metabolismo
Proteína 2 de Membrana Associada ao Lisossomo/metabolismo
Proteínas/metabolismo
[Mh] Termos MeSH secundário: Doença de Alzheimer/genética
Precursor de Proteína beta-Amiloide/genética
Animais
Encéfalo/metabolismo
Córtex Cerebral/metabolismo
Modelos Animais de Doenças
Hipocampo/metabolismo
Seres Humanos
Proteína 2 de Membrana Associada ao Lisossomo/genética
Camundongos
Camundongos Transgênicos
Neurônios/metabolismo
Fragmentos de Peptídeos/metabolismo
alfa-Sinucleína/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amyloid beta-Peptides); 0 (Amyloid beta-Protein Precursor); 0 (Lysosomal-Associated Membrane Protein 2); 0 (Peptide Fragments); 0 (Proteins); 0 (alpha-Synuclein); 0 (lysosomal proteins)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:180124
[Lr] Data última revisão:
180124
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE
[do] DOI:10.1038/mp.2016.189


  6 / 10568 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29227593
[Au] Autor:Sokolik VV; Koliada OK; Shulga SM
[Ti] Título:Effect of ß-amyloid peptide 42 on the dynamics of expression and formation of Аß40, IL -1ß, TNF α, IL -6, IL -10 by peripheral blood mononuclear cells in vitro and its correction by curcumin.
[So] Source:Ukr Biochem J;88(1):109-18, 2016 Jan-Feb.
[Is] ISSN:2409-4943
[Cp] País de publicação:Ukraine
[La] Idioma:eng
[Ab] Resumo:The toxic effect of Аß-oligomers accompanies chronic inflammation, with cytokines as main mediators. Therefore, the cytokine link of inflammation becomes a new target on the way to restrain amyloidosis. The aim of the study was the effect of aggregated Аß42 on the dynamics of expression and formation of endogenous Аß40 and cytokines (IL-1ß, TNFα, IL-6, IL-10) by peripheral blood mononuclear cells in vitro and its correction by curcumin. A suspension of mononuclear cells isolated ex tempore using ficoll-urografin gradient from venous blood samples of healthy volunteers were used to study the effects of Аß42 (15 nM), curcumin (54 pM), and their combined action (at similar concentrations) in time dynamics: 0, 1, 3, 6 and 24 h incubation at 37 °C. Polymerase chain reaction with appropriate primers was used to determine the relative expression of mRNA for AßPP, TNFα, IL-1ß, IL-6, IL-10 and enzyme-linked immunosorbent assay ­ to determine the content of Аß40 and cytokines in mononuclear suspension during all periods of incubation. The individual dynamics AßPP and cytokine expression was shown under the action of the Aß42, which had influence on the content of Aß40, TNFα, IL-1ß, IL-6 and IL-10 in mononuclear suspension. Curcumin displayed the inhibitory effect on gene expression of AßPP, TNFα and IL6, which resulted in the decrease of the level of these two cytokines and Aß40. Thus, the dynamics of anti-inflammatory effect of curcumin in vitro for transcriptional and translational levels of cytokine's formation by mononuclear cells was shown in the work. Direct inhibitory effect of curcumin on the concentration of endogenous Aß40 during the 24 h incubation in conditions of toxic action of Aß42 aggregates was established.
[Mh] Termos MeSH primário: Peptídeos beta-Amiloides/genética
Peptídeos beta-Amiloides/farmacologia
Precursor de Proteína beta-Amiloide/genética
Interleucina-10/genética
Interleucina-1beta/genética
Interleucina-6/genética
Fragmentos de Peptídeos/genética
Fragmentos de Peptídeos/farmacologia
Fator de Necrose Tumoral alfa/genética
[Mh] Termos MeSH secundário: Peptídeos beta-Amiloides/antagonistas & inibidores
Peptídeos beta-Amiloides/imunologia
Precursor de Proteína beta-Amiloide/imunologia
Anti-Inflamatórios não Esteroides/farmacologia
Curcumina/farmacologia
Regulação da Expressão Gênica
Seres Humanos
Interleucina-10/imunologia
Interleucina-1beta/imunologia
Interleucina-6/imunologia
Leucócitos Mononucleares/citologia
Leucócitos Mononucleares/efeitos dos fármacos
Leucócitos Mononucleares/imunologia
Fragmentos de Peptídeos/antagonistas & inibidores
Fragmentos de Peptídeos/imunologia
Cultura Primária de Células
Transdução de Sinais
Fator de Necrose Tumoral alfa/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amyloid beta-Peptides); 0 (Amyloid beta-Protein Precursor); 0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (IL10 protein, human); 0 (IL1B protein, human); 0 (IL6 protein, human); 0 (Interleukin-1beta); 0 (Interleukin-6); 0 (Peptide Fragments); 0 (Tumor Necrosis Factor-alpha); 0 (amyloid beta-protein (1-40)); 0 (amyloid beta-protein (1-42)); 130068-27-8 (Interleukin-10); IT942ZTH98 (Curcumin)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180116
[Lr] Data última revisão:
180116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171212
[St] Status:MEDLINE
[do] DOI:10.15407/ubj88.01.109


  7 / 10568 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29175324
[Au] Autor:Cai HY; Yang JT; Wang ZJ; Zhang J; Yang W; Wu MN; Qi JS
[Ad] Endereço:Department of Microbiology and Immunology, Shanxi Medical University, 56 Xinjian South Road, Taiyuan, Shanxi Province, 030001, China. Electronic address: yancai1@163.com.
[Ti] Título:Lixisenatide reduces amyloid plaques, neurofibrillary tangles and neuroinflammation in an APP/PS1/tau mouse model of Alzheimer's disease.
[So] Source:Biochem Biophys Res Commun;495(1):1034-1040, 2018 01 01.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Type 2 diabetes mellitus (T2DM) has been identified as a high risk factor for Alzheimer's disease (AD). The impairment of insulin signaling has been found in AD brain. Glucagon-like peptide-1 (GLP-1) is an incretin hormone, normalises insulin signaling and acts as a neuroprotective growth factor. We have previously shown that the long-lasting GLP-1 receptor (GLP-1R) agonist lixisenatide plays an important role in memory formation, synaptic plasticity and cell proliferation of rats. In the follow-up study, we analysed the neuroprotective effect and mechanism of lixisenatide, injected for 60 days at 10 nmol/kg i.p. once daily in APP/PS1/tau female mice and C57BL/6J female mice (as control) aged 12 month. The results showed that lixisenatide could reduce amyloid plaques, neurofibrillary tangles and neuroinflammation in the hippocampi of 12-month-old APP/PS1/tau female mice; activation of PKA-CREB signaling pathway and inhibition of p38-MAPK might be the important mechanisms in the neuroprotective function of lixisenatide. The study demonstrated that GLP-1R agonists such as lixisenatide might have the potential to be developed as a novel therapy for AD.
[Mh] Termos MeSH primário: Doença de Alzheimer/tratamento farmacológico
Doença de Alzheimer/metabolismo
Encefalite/tratamento farmacológico
Encefalite/metabolismo
Emaranhados Neurofibrilares/efeitos dos fármacos
Peptídeos/administração & dosagem
[Mh] Termos MeSH secundário: Doença de Alzheimer/patologia
Precursor de Proteína beta-Amiloide/genética
Animais
Relação Dose-Resposta a Droga
Encefalite/patologia
Feminino
Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Emaranhados Neurofibrilares/metabolismo
Emaranhados Neurofibrilares/patologia
Fármacos Neuroprotetores/administração & dosagem
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amyloid beta-Protein Precursor); 0 (Glp1r protein, rat); 0 (Glucagon-Like Peptide-1 Receptor); 0 (Neuroprotective Agents); 0 (Peptides); 74O62BB01U (lixisenatide)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180105
[Lr] Data última revisão:
180105
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE


  8 / 10568 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29216448
[Au] Autor:Huynh TV; Liao F; Francis CM; Robinson GO; Serrano JR; Jiang H; Roh J; Finn MB; Sullivan PM; Esparza TJ; Stewart FR; Mahan TE; Ulrich JD; Cole T; Holtzman DM
[Ad] Endereço:Department of Neurology, Hope Center for Neurological Disorders, Knight Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USA; Medical Scientist Training Program (MSTP), Washington University School of Medicine, St. Louis, MO 63110, USA.
[Ti] Título:Age-Dependent Effects of apoE Reduction Using Antisense Oligonucleotides in a Model of ß-amyloidosis.
[So] Source:Neuron;96(5):1013-1023.e4, 2017 Dec 06.
[Is] ISSN:1097-4199
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The apolipoprotein E (APOE) gene is the strongest genetic risk factor for late-onset Alzheimer disease. Previous studies suggest that reduction of apoE levels through genetic manipulation can reduce Aß pathology. However, it is not clear how reduction of apoE levels after birth would affect amyloid deposition. We utilize an antisense oligonucleotide (ASO) to reduce apoE expression in the brains of APP/PS1-21 mice homozygous for the APOE-ε4 or APOE-ε3 allele. ASO treatment starting after birth led to a significant decrease in Aß pathology when assessed at 4 months. Interestingly, ASO treatment starting at the onset of amyloid deposition led to an increase in Aß plaque size and a reduction in plaque-associated neuritic dystrophy with no change in overall plaque load. These results suggest that lowering apoE levels prior to plaque deposition can strongly affect the initiation of Aß pathology while lowering apoE after Aß seeding modulates plaque size and toxicity.
[Mh] Termos MeSH primário: Peptídeos beta-Amiloides
Amiloidose/tratamento farmacológico
Apolipoproteínas E/antagonistas & inibidores
Oligonucleotídeos Antissenso/uso terapêutico
[Mh] Termos MeSH secundário: Envelhecimento/fisiologia
Alelos
Doença de Alzheimer/patologia
Precursor de Proteína beta-Amiloide/biossíntese
Precursor de Proteína beta-Amiloide/genética
Amiloidose/patologia
Animais
Apolipoproteína E3/genética
Apolipoproteína E4/genética
Seres Humanos
Masculino
Camundongos
Camundongos Transgênicos
Placa Amiloide/patologia
Placa Amiloide/prevenção & controle
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amyloid beta-Peptides); 0 (Amyloid beta-Protein Precursor); 0 (Apolipoprotein E3); 0 (Apolipoprotein E4); 0 (Apolipoproteins E); 0 (Oligonucleotides, Antisense)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171220
[Lr] Data última revisão:
171220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE


  9 / 10568 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29176903
[Au] Autor:Chu TH; Cummins K; Sparling JS; Tsutsui S; Brideau C; Nilsson KPR; Joseph JT; Stys PK
[Ad] Endereço:Hotchkiss Brain Institute, Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.
[Ti] Título:Axonal and myelinic pathology in 5xFAD Alzheimer's mouse spinal cord.
[So] Source:PLoS One;12(11):e0188218, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:As an extension of the brain, the spinal cord has unique properties which could allow us to gain a better understanding of CNS pathology. The brain and cord share the same cellular components, yet the latter is simpler in cytoarchitecture and connectivity. In Alzheimer's research, virtually all focus is on brain pathology, however it has been shown that transgenic Alzheimer's mouse models accumulate beta amyloid plaques in spinal cord, suggesting that the cord possesses the same molecular machinery and conditions for plaque formation. Here we report a spatial-temporal map of plaque load in 5xFAD mouse spinal cord. We found that plaques started to appear at 11 weeks, then exhibited a time dependent increase and differential distribution along the cord. More plaques were found in cervical than other spinal levels at all time points examined. Despite heavy plaque load at 6 months, the number of cervical motor neurons in 5xFAD mice is comparable to wild type littermates. On detailed microscopic examination, fine beta amyloid-containing and beta sheet-rich thread-like structures were found in the peri-axonal space of many axons. Importantly, these novel structures appear before any plaque deposits are visible in young mice spinal cord and they co-localize with axonal swellings at later stages, suggesting that these thread-like structures might represent the initial stages of plaque formation, and could play a role in axonal damage. Additionally, we were able to demonstrate increasing myelinopathy in aged 5xFAD mouse spinal cord using the lipid probe Nile Red with high resolution. Collectively, we found significant amyloid pathology in grey and white matter of the 5xFAD mouse spinal cord which indicates that this structure maybe a useful platform to study mechanisms of Alzheimer's pathology and disease progression.
[Mh] Termos MeSH primário: Doença de Alzheimer/patologia
Axônios/patologia
Bainha de Mielina/patologia
Medula Espinal/patologia
[Mh] Termos MeSH secundário: Envelhecimento
Precursor de Proteína beta-Amiloide/metabolismo
Animais
Substância Cinzenta/patologia
Seres Humanos
Camundongos Transgênicos
Neurônios Motores/patologia
Neuroglia/patologia
Placa Amiloide/patologia
Substância Branca/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amyloid beta-Protein Precursor)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171219
[Lr] Data última revisão:
171219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188218


  10 / 10568 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:29176823
[Au] Autor:Dursun E; Gezen-Ak D
[Ad] Endereço:Brain and Neurodegenerative Disorders Research Laboratory, Department of Medical Biology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey.
[Ti] Título:Vitamin D receptor is present on the neuronal plasma membrane and is co-localized with amyloid precursor protein, ADAM10 or Nicastrin.
[So] Source:PLoS One;12(11):e0188605, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Our recent study indicated that vitamin D and its receptors are important parts of the amyloid processing pathway in neurons. Yet the role of vitamin D receptor (VDR) in amyloid pathogenesis is complex and all regulations over the production of amyloid beta cannot be explained solely with the transcriptional regulatory properties of VDR. Given that we hypothesized that VDR might exist on the neuronal plasma membrane in close proximity with amyloid precursor protein (APP) and secretase complexes. The present study primarily focused on the localization of VDR in neurons and its interaction with amyloid pathology-related proteins. The localization of VDR on neuronal membranes and its co-localization with target proteins were investigated with cell surface staining followed by immunofluorescence labelling. The FpClass was used for protein-protein interaction prediction. Our results demonstrated the localization of VDR on the neuronal plasma membrane and the co-localization of VDR and APP or ADAM10 or Nicastrin and limited co-localization of VDR and PS1. E-cadherin interaction with APP or the γ-secretase complex may involve NOTCH1, NUMB, or FHL2, according to FpClass. This suggested complex might also include VDR, which greatly contributes to Ca+2 hemostasis with its ligand vitamin D. Consequently, we suggested that VDR might be a member of this complex also with its own non-genomic action and that it can regulate the APP processing pathway in this way in neurons.
[Mh] Termos MeSH primário: Proteína ADAM10/metabolismo
Secretases da Proteína Precursora do Amiloide/metabolismo
Precursor de Proteína beta-Amiloide/metabolismo
Membrana Celular/metabolismo
Glicoproteínas de Membrana/metabolismo
Neurônios/metabolismo
Receptores de Calcitriol/metabolismo
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Mapeamento de Interação de Proteínas
Transporte Proteico
Ratos Sprague-Dawley
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amyloid beta-Protein Precursor); 0 (Membrane Glycoproteins); 0 (Receptors, Calcitriol); 0 (nicastrin protein); EC 3.4.- (Amyloid Precursor Protein Secretases); EC 3.4.24.81 (ADAM10 Protein)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171219
[Lr] Data última revisão:
171219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188605



página 1 de 1057 ir para página                         
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde