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https://www.readbyqxmd.com/read/29036903/resveratrol-and-amyloid-beta-mechanistic-insights
#1
REVIEW
Yongming Jia, Na Wang, Xuewei Liu
The amyloid-beta (Aβ) hypothesis that dyshomeostasis between Aβ production and clearance is a very early, key molecular factor in the etiology of Alzheimer's disease (AD) has been proposed and examined in the AD research field. Scientists have focused on seeking natural products or drugs to influence the dynamic equilibrium of Aβ, targeting production and clearance of Aβ. There is emerging evidence that resveratrol (Res), a naturally occurring polyphenol mainly found in grapes and red wine, acts on AD in numerous in vivo and in vitro models...
October 14, 2017: Nutrients
https://www.readbyqxmd.com/read/29036881/comparison-of-in-vitro-assays-in-selecting-radiotracers-for-in-vivo-p-glycoprotein-pet-imaging
#2
Renske M Raaphorst, Heli Savolainen, Mariangela Cantore, Evita van de Steeg, Aren van Waarde, Nicola A Colabufo, Philip H Elsinga, Adriaan A Lammertsma, Albert D Windhorst, Gert Luurtsema
Positron emission tomography (PET) imaging of P-glycoprotein (P-gp) in the blood-brain barrier can be important in neurological diseases where P-gp is affected, such as Alzheimer´s disease. Radiotracers used in the imaging studies are present at very small, nanomolar, concentration, whereas in vitro assays where these tracers are characterized, are usually performed at micromolar concentration, causing often discrepant in vivo and in vitro data. We had in vivo rodent PET data of [(11)C]verapamil, (R)-N-[(18)F]fluoroethylverapamil, (R)-O-[(18)F]fluoroethyl-norverapamil, [(18)F]MC225 and [(18)F]MC224 and we included also two new molecules [(18)F]MC198 and [(18)F]KE64 in this study...
September 20, 2017: Pharmaceuticals
https://www.readbyqxmd.com/read/29036823/prevalence-and-correlates-of-behavioral-disorders-in-old-age-subjects-with-cognitive-impairment-results-from-the-regal-project
#3
Virginia Boccardi, Manuela Conestabile Della Staffa, Marta Baroni, Sara Ercolani, Michele Francesco Croce, Carmelinda Ruggiero, Patrizia Mecocci
BACKGROUND: Presence of behavioral and psychological symptoms of dementia (BPSD) is very common in subjects with cognitive impairment, representing an important determinant of disease progression, institutionalization, and worse prognosis. Knowledge of the prevalence and correlates of BPSD in community-living old subjects with cognitive impairment is limited so far, but it is essential for establishing specifically tailored care and cure in such a vulnerable population. OBJECTIVE: With this study, we aimed at investigating, in a large sample of old age subjects with cognitive impairment, BPSD prevalence and correlates including the main demographic, clinical, and socio-environmental characteristics...
October 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29036814/curcumin-ameliorates-neuroinflammation-neurodegeneration-and-memory-deficits-in-p25-transgenic-mouse-model-that-bears-hallmarks-of-alzheimer-s-disease
#4
Jeyapriya Raja Sundaram, Charlene Priscilla Poore, Noor Hazim Bin Sulaimee, Tej Pareek, Wei Fun Cheong, Markus R Wenk, Harish C Pant, Sally A Frautschy, Chian-Ming Low, Sashi Kesavapany
Several studies have indicated that neuroinflammation is indeed associated with neurodegenerative disease pathology. However, failures of recent clinical trials of anti-inflammatory agents in neurodegenerative disorders have emphasized the need to better understand the complexity of the neuroinflammatory process in order to unravel its link with neurodegeneration. Deregulation of Cyclin-dependent kinase 5 (Cdk5) activity by production of its hyperactivator p25 is involved in the formation of tau and amyloid pathology reminiscent of Alzheimer's disease (AD)...
October 12, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29035083/multiplicity-adjusted-semiparametric-benefiting-subgroup-identification-in-clinical-trials
#5
Patrick M Schnell, Peter Müller, Qi Tang, Bradley P Carlin
Background A recent focus in the health sciences has been the development of personalized medicine, which includes determining the population for which a given treatment is effective. Due to limited data, identifying the true benefiting population is a challenging task. To tackle this difficulty, the credible subgroups approach provides a pair of bounding subgroups for the true benefiting subgroup, constructed so that one is contained by the benefiting subgroup while the other contains the benefiting subgroup with high probability...
October 1, 2017: Clinical Trials: Journal of the Society for Clinical Trials
https://www.readbyqxmd.com/read/29034965/role-of-serum-albumin-as-a-nanoparticulate-carrier-for-nose-to-brain-delivery-of-r-flurbiprofen-implications-for-the-treatment-of-alzheimer-s-disease
#6
Ling Rong Wong, Paul C Ho
OBJECTIVES: R-flurbiprofen (R-FP) was found to offer neuroprotective effects by inhibiting mitochondrial calcium overload induced by β-amyloid peptide toxicity in Alzheimer's disease (AD). However, poor brain penetration after oral administration posed a challenge to its further development for AD treatment. In this study, we investigated the potential of serum albumin as nanoparticulate carriers for nose-to-brain delivery of R-FP to improve its brain accumulation. METHODS: Mice were subjected to three treatment groups: (1) intranasal R-FP solution, (2) oral R-FP solution and (3) intranasal R-FP albumin nanoparticles...
October 16, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/29034839/pharmacogenetics-of-angiotensin-converting-enzyme-inhibitors-in-patients-with-alzheimer-s-disease-dementia
#7
Fabricio Ferreira de Oliveira, Elizabeth Suchi Chen, Marilia Cardoso Smith, Paulo Henrique Ferreira Bertolucci
BACKGROUND: While the angiotensin-converting enzyme degrades amyloid-β, angiotensin-converting enzyme inhibitors (ACEis) may slow cognitive decline by way of cholinergic effects, by increasing brain substance P and boosting the activity of neprilysin, and by modulating glucose homeostasis and augmenting the secretion of adipokines to enhance insulin sensitivity in patients with Alzheimer's disease dementia (AD). We aimed to investigate whether ACE gene polymorphisms rs1800764 and rs4291 are associated with cognitive and functional change in patients with AD, while also taking APOE haplotypes and anti-hypertensive treatment with ACEis into account for stratification...
October 16, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/29034183/alzheimer-disease-clues-from-traditional-and-complementary-medicine
#8
REVIEW
Edwin L Cooper, Melissa J Ma
Despite modern medicine's incredible innovation and resulting accumulation of valuable knowledge, many of the world's most problematic diseases such as Alzheimer Disease (AD) still lack effective cures and treatments. Western medicine has revealed many genetic, cellular, and molecular processes that characterize AD such as protein aggregation and inflammation. As the need for novel and effective treatments increases, researchers have turned towards traditional medicine as a resource. Modern, evidence based research examining traditional and complementary remedies for AD has generated promising results within the last decade...
October 2017: Journal of Traditional and Complementary Medicine
https://www.readbyqxmd.com/read/29033972/clinical-spectrum-risk-factors-and-behavioral-abnormalities-among-dementia-subtypes-in-a-north-indian-population-a-hospital-based-study
#9
Suman Kushwaha, Puneet Talwar, Aldrin Anthony, Meena Gupta, Kiran Bala, Rachna Agarwal, Vibha Sharma, Ritushree Kukreti
BACKGROUND: As variability in the clinical profile of dementia subtypes had been reported with regional differences across the world, we conducted a retrospective hospital-based study in a North Indian population. METHODS: We retrieved patient records from 2007 to 2014 for details of clinical evaluation, diagnosis, neuroimaging, biochemical investigations, and follow-up of 1,876 patients with dementia (PwD), and the data were analyzed using descriptive statistics...
May 2017: Dementia and Geriatric Cognitive Disorders Extra
https://www.readbyqxmd.com/read/29033786/wnt5a-promotes-cortical-neuron-survival-by-inhibiting-cell-cycle-activation
#10
Li Zhou, Di Chen, Xu-Ming Huang, Fei Long, Hua Cai, Wen-Xia Yao, Zhong-Cheng Chen, Zhi-Jian Liao, Zhe-Zhi Deng, Sha Tan, Yi-Long Shan, Wei Cai, Yu-Ge Wang, Ri-Hong Yang, Nan Jiang, Tao Peng, Ming-Fan Hong, Zheng-Qi Lu
β-Amyloid protein (Aβ) is thought to cause neuronal loss in Alzheimer's disease (AD). Aβ treatment promotes the re-activation of a mitotic cycle and induces rapid apoptotic death of neurons. However, the signaling pathways mediating cell-cycle activation during neuron apoptosis have not been determined. We find that Wnt5a acts as a mediator of cortical neuron survival, and Aβ42 promotes cortical neuron apoptosis by downregulating the expression of Wnt5a. Cell-cycle activation is mediated by the reduced inhibitory effect of Wnt5a in Aβ42 treated cortical neurons...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29033233/design-synthesis-and-biological-evaluation-of-2-acetyl-5-o-amino-alkyl-phenol-derivatives-as-multifunctional-agents-for-the-treatment-of-alzheimer-s-disease
#11
Zhipei Sang, Keren Wang, Huifang Wang, Huijuan Wang, Qianwen Ma, Xue Han, Mengyao Ye, Lintao Yu, Wenmin Liu
A series of 2-acetyl-5-O-(amino-alkyl)phenol derivatives was designed, synthesized and evaluated as multi-function inhibitors for the treatment of Alzheimer's disease (AD). The results revealed that compound TM-3 indicated selective AChE inhibitory potency (eeAChE, IC50 = 0.69 μM, selective index (SI) = 32.7). Both kinetic analysis of AChE inhibition and molecular modeling study suggested that TM-3 could simultaneously bind to the catalytic active site and peripheral anionic site of AChE. And TM-3 was also a highly selective MAO-B inhibitor (IC50 = 6...
September 28, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29033232/design-synthesis-and-biological-evaluation-of-phthalimide-alkylamine-derivatives-as-balanced-multifunctional-cholinesterase-and-monoamine-oxidase-b-inhibitors-for-the-treatment-of-alzheimer-s-disease
#12
Zhipei Sang, Keren Wang, Huifang Wang, Lintao Yu, Huijuan Wang, Qianwen Ma, Mengyao Ye, Xue Han, Wenmin Liu
A series of novel phthalimide-alkylamine derivatives were synthesized and evaluated as multi-functions inhibitors for the treatment of Alzheimer's disease (AD). The results showed that compound TM-9 could be regarded as a balanced multi-targets active molecule. It exhibited potent and balanced inhibitory activities against ChE and MAO-B (huAChE, huBuChE, and huMAO-B with IC50 values of 1.2μM, 3.8μM and 2.6 μM, respectively) with low selectivity. Both kinetic analysis of AChE inhibition and molecular modeling study suggested that TM-9 binds simultaneously to the catalytic active site and peripheral anionic site of AChE...
September 28, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29032765/recent-patent-advances-for-neurodegenerative-disorders-and-its-treatment
#13
Bhavna Kumar, Deepika Sharma
BACKGROUND: Neurodegenerative disorders are one of the common diseases that affect our society with tremendous medical and financial burdens. As a whole, neurodegeneration affects individuals of all ages, but becomes increasingly frequent with age, coming to affect a very large share of our elderly population which is severely affecting the patient, caregivers, and enormously increasing the financial burden of the nation. These diseases share a very complex nature, which often result from combined genetic, environment and pathogenic factors...
October 10, 2017: Recent Patents on Drug Delivery & Formulation
https://www.readbyqxmd.com/read/29031088/probing-the-correlation-of-neuronal-loss-neurofibrillary-tangles-and-cell-death-markers-across-the-alzheimer-s-disease-braak-stages-a-quantitative-study-in-humans
#14
Panos Theofilas, Alexander J Ehrenberg, Austin Nguy, Julia M Thackrey, Sara Dunlop, Maria B Mejia, Ana T Alho, Renata Elaine Paraizo Leite, Roberta Diehl Rodriguez, Claudia K Suemoto, Camila F Nascimento, Marcus Chin, Daniel Medina-Cleghorn, Ana Maria Cuervo, Michelle Arkin, William W Seeley, Bruce L Miller, Ricardo Nitrini, Carlos Augusto Pasqualucci, Wilson Jacob Filho, Udo Rueb, John Neuhaus, Helmut Heinsen, Lea T Grinberg
Clarifying the mechanisms connecting neurofibrillary tangle (NFT) neurotoxicity to neuronal dysfunction in humans is likely to be pivotal for developing effective treatments for Alzheimer's disease (AD). To model the temporal progression of AD in humans, we used a collection of brains with controls and individuals from each Braak stage to quantitatively investigate the correlation between intraneuronal caspase activation or macroautophagy markers, NFT burden, and neuronal loss, in the dorsal raphe nucleus and locus coeruleus, the earliest vulnerable areas to NFT accumulation...
September 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29031071/discovery-of-thienopyrrolotriazine-derivatives-to-protect-mitochondrial-function-against-a%C3%AE-induced-neurotoxicity
#15
TaeHun Kim, Woo Seung Son, Mohammad Neaz Morshed, Ashwini M Londhe, Seo Yun Jung, Jong-Hyun Park, Woo-Kyu Park, Sang Min Lim, Ki Duk Park, Sung Jin Cho, Kyu-Sung Jeong, Jiyoun Lee, Ae Nim Pae
Recovery of mitochondrial dysfunction has gained increasing attention as an alternative therapeutic strategy for Alzheimer's disease (AD). Recent studies suggested that the 18 kDa mitochondrial translocator protein (TSPO) has the potential to serve as a drug target for the treatment of AD. In this study, we generated a structure-based pharmacophore model and virtually screened a commercial library, identifying SVH07 as a virtual hit, which contained a tricyclic core structure, thieno[2',3':4,5]pyrrolo[1,2-d][1,2,4]triazine group...
September 21, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29030286/peptides-acting-as-cognitive-enhancers
#16
Diego Asua, Ghassen Bougamra, María Calleja, Miguel Morales, Shira Knafo
The aim of this paper is to present an overview of three peptides that, by improving synaptic function, enhance learning and memory in laboratory rodents. We summarize their structure, their mechanisms of action, and their effects on synaptic and cognitive function. First we describe FGL, a peptide derived from the neural cell adhesion molecule which improves cognition by the activation of the PKC pathway that triggers an activity-dependent delivery of AMPA receptors to the synapses. Then we describe PTD4-PI3KAc peptide that by activating PI3K signalling pathway it promotes synapse and spine formation and enhances hippocampal dependent memory...
October 10, 2017: Neuroscience
https://www.readbyqxmd.com/read/29026940/advanced-bioanalytics-for-precision-medicine
#17
Aldo Roda, Elisa Michelini, Cristiana Caliceti, Massimo Guardigli, Mara Mirasoli, Patrizia Simoni
Precision medicine is a new paradigm that combines diagnostic, imaging, and analytical tools to produce accurate diagnoses and therapeutic interventions tailored to the individual patient. This approach stands in contrast to the traditional "one size fits all" concept, according to which researchers develop disease treatments and preventions for an "average" patient without considering individual differences. The "one size fits all" concept has led to many ineffective or inappropriate treatments, especially for pathologies such as Alzheimer's disease and cancer...
October 12, 2017: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/29026707/nadph-oxidase-mediates-%C3%AE-amyloid-peptide-induced-neuronal-death-in-mouse-cortical-cultures
#18
Kee-Oh Chay, Kyoung Young Nam Koong, Shinae Hwang, Jong-Keun Kim, Choon Sang Bae
β-Amyloid peptide (Aβ) is the main component of senile plaques in patients with Alzheimer's disease, and is known to be a main pathogenic factor of the disease. Recent evidence indicates that activation of NADPH oxidase (NOX) in microglia or astrocytes may be a source of Aβ-induced reactive oxygen species (ROS). We investigated the role of neuronal NOX in Aβ-induced neuronal death in mouse mixed cortical cultures. Cell death was assessed by measuring lactate dehydrogenase efflux to bathing media 24 or 48 hr after exposure to Aβ25-35, a fragment of Aβ with an equivalent neurotoxic effect...
September 2017: Chonnam Medical Journal
https://www.readbyqxmd.com/read/29026042/scalable-synthesis-of-bryostatin-1-and-analogs-adjuvant-leads-against-latent-hiv
#19
Paul A Wender, Clayton T Hardman, Stephen Ho, Matthew S Jeffreys, Jana K Maclaren, Ryan V Quiroz, Steven M Ryckbosch, Akira J Shimizu, Jack L Sloane, Matthew C Stevens
Bryostatin 1 is an exceedingly scarce marine-derived natural product that is in clinical development directed at HIV/AIDS eradication, cancer immunotherapy, and the treatment of Alzheimer's disease. Despite this unique portfolio of indications, its availability has been limited and variable, thus impeding research and clinical studies. Here, we report a total synthesis of bryostatin 1 that proceeds in 29 total steps (19 in the longest linear sequence, >80% average yield per step), collectively produces grams of material, and can be scaled to meet clinical needs (~20 grams per year)...
October 13, 2017: Science
https://www.readbyqxmd.com/read/29024570/deuterium-reinforced-polyunsaturated-fatty-acids-improve-cognition-in-a-mouse-model-of-sporadic-alzheimer-s-disease
#20
Ahmed Elharram, Nicole M Czegledy, Michael Golod, Ginger L Milne, Erik Pollock, Brian M Bennett, Mikhail S Shchepinov
Oxidative damage resulting from increased lipid peroxidation (LPO) is considered an important factor in the development of late onset/age-related Alzheimer's disease (AD). Deuterium-reinforced polyunsaturated fatty acids (D-PUFAs) are more resistant to the reactive oxygen species-initiated chain reaction of LPO than regular hydrogenated (H-) PUFAs. We investigated the effect of D-PUFA treatment on LPO and cognitive performance in aldehyde dehydrogenase 2 (Aldh2) null mice, an established model of oxidative stress-related cognitive impairment that exhibits AD-like pathologies...
October 12, 2017: FEBS Journal
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