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Alzheimers disease treatment

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https://www.readbyqxmd.com/read/27926950/c6-and-c7-substituted-3-4-dihydro-2-1h-quinolinones-as-inhibitors-of-monoamine-oxidase
#1
L Meiring, J Petzer, A Petzer
Purpose Monoamine oxidase (MAO) inhibitors are considered to be useful therapeutic agents and isoform specific inhibitors are employed for the treatment of depression and Parkinson's disease. MAO inhibitors are also under investigation for the treatment of disorders ranging from Alzheimer's disease, prostate cancer and certain cardiomyopathies. While a number of irreversible MAO inhibitors are available in the clinic, reversible inhibitors, particularly of the MAO-B isoform are still being developed. Based on our interest in discovering reversible inhibitors with specificity for MAO-B, we have recently reported that, among a series of 10 3,4-dihydro-2(1H)-quinolinone derivatives, are high potency MAO-B inhibitors, with a number of homologues displaying good selectivities for MAO-B over the MAO-A isoform...
December 7, 2016: Drug Research
https://www.readbyqxmd.com/read/27926574/neural-activity-memory-and-dementias-serotonergic-markers
#2
Alfredo Meneses
Dysfunctional memory seems to be a key component of diverse dementias and other neuropsychiatric disorders; unfortunately, no effective treatment exists for this, probably because of the absence of neural biomarkers accompanying it. Diverse neurotransmission systems have been implicated in memory, including serotonin or 5-hydroxytryptamine (5-HT). There are multiple serotonergic pharmacological tools, well-characterized downstream signaling in mammals' species and neural markers providing new insights into memory functions and dysfunctions...
December 6, 2016: Behavioural Pharmacology
https://www.readbyqxmd.com/read/27926449/the-role-of-dopamine-in-the-pathophysiology-and-treatment-of-apathy
#3
T T-J Chong, M Husain
Disorders of diminished motivation, such as apathy, are common and prevalent across a wide range of medical conditions, including Parkinson's disease, Alzheimer's dementia, stroke, depression, and schizophrenia. Such disorders have a significant impact on morbidity and quality of life, yet their management lacks consensus and remains unsatisfactory. Here, we review laboratory and clinical evidence for the use of dopaminergic therapies in the treatment of apathy. Dopamine is a key neurotransmitter that regulates motivated decision making in humans and other species...
2016: Progress in Brain Research
https://www.readbyqxmd.com/read/27924507/tppu-protects-tau-from-h2o2-induced-hyperphosphorylation-in-hek293-tau-cells-by-regulating-pi3k-akt-gsk-3%C3%AE-pathway
#4
En-Sheng Yao, Yan Tang, Xing-Hua Liu, Ming-Huan Wang
Neurofibrillary pathology of abnormally hyperphosphorylated tau is a hallmark of Alzheimer's disease (AD) and other tauopathies. Phosphatidylinositol 3-kinase (PI3K)/Akt/glycogen synthase kinase-3 beta (GSK-3β) signaling pathway is pivotal for tau phosphorylation. Inhibition of soluble epoxide hydrolase (sEH) metabolism has been shown to effectively increase the accumulation of epoxyeicosatrienoic acids (EETs), which are cytochrome P450 metabolites of arachidonic acid and have been demonstrated to have neuroprotective effects...
December 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/27923632/puerarin-suppression-of-a%C3%AE-1-42-induced-primary-cortical-neuron-death-is-largely-dependent-on-er%C3%AE
#5
Li Li, Zuguang Xue, Lei Chen, Xueyu Chen, Heshuang Wang, Xiaobo Wang
Recent study has suggested that estrogen replacement therapy (ERT) can decrease the risk of the development of Alzheimer's disease (AD), and phytoestrogen has been proposed as a potential alternative to ERT. In this study, we investigated the protective function of puerarin (a phytoestrogen isolated from puerarin lobate) against amyloid beta (Aβ1-42)-induced toxicity in cortical neurons and established the connection between such a protection and estrogen receptor (ER) activation. Puerarin suppressed Aβ1-42-induced cortical neuron death in a concentration-dependent manner...
December 3, 2016: Brain Research
https://www.readbyqxmd.com/read/27923524/the-therapeutic-potential-of-metabolic-hormones-in-the-treatment-of-age-related-cognitive-decline-and-alzheimer-disease
#6
REVIEW
John Grizzanti, Hyoung-Gon Lee, Antoni Camins, Merce Pallas, Gemma Casadesus
Aging leads to a number of physiological alterations, specifically changes in circulating hormone levels, increases in fat deposition, decreases in metabolism, changes in inflammatory responses, and reductions in growth factors. These progressive changes in physiology and metabolism are exacerbated by modern culture and Western diet and give rise to diseases such as obesity, metabolic syndrome, and type 2 (non-insulin-dependent) diabetes (T2D). These age and lifestyle-related metabolic diseases are often accompanied by insulin and leptin resistance, as well as aberrant amylin production and signaling...
November 8, 2016: Nutrition Research
https://www.readbyqxmd.com/read/27922847/apolipoprotein-e-metabolism-and-functions-in-brain-and-its-role-in-alzheimer-s-disease
#7
Fan Liao, Hyejin Yoon, Jungsu Kim
PURPOSE OF REVIEW: APOE4 genotype is the strongest genetic risk factor for Alzheimer's disease. Prevailing evidence suggests that amyloid β plays a critical role in Alzheimer's disease. The objective of this article is to review the recent findings about the metabolism of apolipoprotein E (ApoE) and amyloid β and other possible mechanisms by which ApoE contributes to the pathogenesis of Alzheimer's disease. RECENT FINDINGS: ApoE isoforms have differential effects on amyloid β metabolism...
December 5, 2016: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/27920795/donepezil-enhances-frontal-functional-connectivity-in-alzheimer-s-disease-a-pilot-study
#8
Ludovica Griffanti, Gordon K Wilcock, Natalie Voets, Guendalina Bonifacio, Clare E Mackay, Mark Jenkinson, Giovanna Zamboni
BACKGROUND: We have previously shown that increased resting-state functional magnetic resonance imaging (fMRI)-based functional connectivity (FC) within the frontal resting-state networks in Alzheimer's disease (AD) patients reflects residual, possibly compensatory, function. This suggests that symptomatic treatments should aim to enhance FC specifically in these networks. METHODS: 18 patients with probable AD underwent brain MRI and neuropsychological assessment at baseline and after 12 weeks of treatment with donepezil...
September 2016: Dementia and Geriatric Cognitive Disorders Extra
https://www.readbyqxmd.com/read/27920671/proceedings-of-the-fourth-annual-deep-brain-stimulation-think-tank-a-review-of-emerging-issues-and-technologies
#9
Wissam Deeb, James J Giordano, Peter J Rossi, Alon Y Mogilner, Aysegul Gunduz, Jack W Judy, Bryan T Klassen, Christopher R Butson, Craig Van Horne, Damiaan Deny, Darin D Dougherty, David Rowell, Greg A Gerhardt, Gwenn S Smith, Francisco A Ponce, Harrison C Walker, Helen M Bronte-Stewart, Helen S Mayberg, Howard J Chizeck, Jean-Philippe Langevin, Jens Volkmann, Jill L Ostrem, Jonathan B Shute, Joohi Jimenez-Shahed, Kelly D Foote, Aparna Wagle Shukla, Marvin A Rossi, Michael Oh, Michael Pourfar, Paul B Rosenberg, Peter A Silburn, Coralie de Hemptine, Philip A Starr, Timothy Denison, Umer Akbar, Warren M Grill, Michael S Okun
This paper provides an overview of current progress in the technological advances and the use of deep brain stimulation (DBS) to treat neurological and neuropsychiatric disorders, as presented by participants of the Fourth Annual DBS Think Tank, which was convened in March 2016 in conjunction with the Center for Movement Disorders and Neurorestoration at the University of Florida, Gainesveille FL, USA. The Think Tank discussions first focused on policy and advocacy in DBS research and clinical practice, formation of registries, and issues involving the use of DBS in the treatment of Tourette Syndrome...
2016: Frontiers in Integrative Neuroscience
https://www.readbyqxmd.com/read/27919712/extracts-from-two-ubiquitous-mediterranean-plants-ameliorate-cellular-and-animal-models-of-neurodegenerative-proteinopathies
#10
Michelle Briffa, Stephanie Ghio, Johanna Neuner, Alison J Gauci, Rebecca Cacciottolo, Christelle Marchal, Mario Caruana, Christophe Cullin, Neville Vassallo, Ruben J Cauchi
A signature feature of age-related neurodegenerative proteinopathies is the misfolding and aggregation of proteins, typically amyloid-β (Aβ) in Alzheimer's disease (AD) and α-synuclein (α-syn) in Parkinson's disease (PD), into soluble oligomeric structures that are highly neurotoxic. Cellular and animal models that faithfully replicate the hallmark features of these disorders are being increasing exploited to identify disease-modifying compounds. Natural compounds have been identified as a useful source of bioactive molecules with promising neuroprotective capabilities...
December 2, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27916702/chronic-kidney-disease-accelerates-cognitive-impairment-in-a-mouse-model-of-alzheimer-s-disease-through-angiotensin-ii
#11
Takashi Nakagawa, Yu Hasegawa, Ken Uekawa, Shokei Kim-Mitsuyama
Epidemiological studies suggest that chronic kidney disease (CKD) is a significant risk factor in the development of cognitive decline. However, the exact role of CKD in cognitive impairment or dementia is unclear. This work was performed to examine the potential impact of CKD on cognitive impairment in Alzheimer's disease (AD), focusing on angiotensin II. (1) CKD was induced in 5XFAD mice, an AD model mouse, and wild-type mice by feeding adenine-containing diet and the effect on cognitive function was compared between both strains...
December 1, 2016: Experimental Gerontology
https://www.readbyqxmd.com/read/27915995/lack-of-p-glycoprotein-results-in-impairment-of-removal-of-beta-amyloid-and-increased-intraparenchymal-cerebral-amyloid-angiopathy-after-active-immunization-in-a-transgenic-mouse-model-of-alzheimer-s-disease
#12
Sascha Brückmann, Anja Brenn, Markus Grube, Katharina Niedrig, Silva Holtfreter, Oliver von Bohlen Und Halbach, Martin Groschup, Markus Keller, Silke Vogelgesang
Immunization against beta-amyloid (Aβ) reduces cerebral Aβ deposits and improves cognitive capacities in transgenic mouse models, and thus has been considered a promising disease-modifying therapeutic approach for Alzheimer's disease (AD). Although clinical trials in AD patients have yielded evidence for clearance of parenchymal Aβ plaques, Aβ increases in blood vessels of treated patients. We hypothesize that an age-related decline in the mechanisms that clear Aβ from the brain might be at least in part responsible for the failure to purge and re-distribute Aβ...
December 1, 2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/27915121/predicting-individual-brain-functional-connectivity-using-a-bayesian-hierarchical-model
#13
Tian Dai, Ying Guo
Network-oriented analysis of functional magnetic resonance imaging (fMRI), especially resting-state fMRI, has revealed important association between abnormal connectivity and brain disorders such as schizophrenia, major depression and Alzheimer's disease. Imaging-based brain connectivity measures have become a useful tool for investigating the pathophysiology, progression and treatment response of psychiatric disorders and neurodegenerative diseases. Recent studies have started to explore the possibility of using functional neuroimaging to help predict disease progression and guide treatment selection for individual patients...
November 30, 2016: NeuroImage
https://www.readbyqxmd.com/read/27915007/effect-of-the-oral-administration-of-nanoencapsulated-quercetin-on-a-mouse-model-of-alzheimer-s-disease
#14
Lina Clara Gayoso E Almendra Ibiapina, Elena Puerta, José Eduardo Suárez-Santiago, Nereide Stela Santos-Magalhães, Maria J Ramirez, Juan M Irache
Quercetin has been identified as a promising compound with a neuroprotective potential against age-related neurodegenerative diseases such as Alzheimer's disease (AD). Nevertheless, the clinical application of quercetin is hampered by its low oral bioavailability. The aim of this work was to evaluate the capability of nanoencapsulated quercetin in zein nanoparticles (NPQ), that significantly improves the oral absorption and bioavailability of the flavonoid, as potential oral treatment for AD. For this purpose, SAMP8 mice were orally treated for two months with either NPQ (25mg/kg every 48hours) or a solution of quercetin (Q; 25mg/kg daily)...
November 30, 2016: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/27914953/both-secreted-and-the-cellular-levels-of-bdnf-attenuated-due-to-tau-hyperphosphorylation-in-primary-cultures-of-cortical-neurons
#15
İrem Lütfiye Atasoy, Erdinç Dursun, Duygu Gezen Ak, Derya Metin Armağan, Melek Öztürk, Selma Yılmazer
Intracellular aggregation of hyperphosphorylated tau in neurofibrillary tangles (NFTs) is a major neuropathological hallmark of taupathies such as Alzheimer's disease. Okadaic acid (OKA) is a potent inhibitor of PP2A, leading to abnormal tau phosphorylation. Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is selectively downregulated in AD. In this study, we investigated the effects of OKA induced tau hyperphosphorylation on secreted and cellular levels of BDNF in primary cortical neurons that were treated with 25nM OKA...
November 30, 2016: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/27914038/serotonin-5-ht6-receptor-antagonists-in-alzheimer-s-disease-therapeutic-rationale-and-current-development-status
#16
Hilda Ferrero, Maite Solas, Paul T Francis, Maria J Ramirez
Alzheimer's disease (AD) is the most common cause of dementia in elderly people. Because of the lack of effective treatments for this illness, research focused on identifying compounds that restore cognition and functional impairments in patients with AD is a very active field. Since its discovery in 1993, the serotonin 5-HT6 receptor has received increasing attention, and a growing number of studies supported 5-HT6 receptor antagonism as a target for improving cognitive dysfunction in AD. This article reviews the rationale behind investigations into the targeting of 5-HT6 receptors as a symptomatic treatment for cognitive and/or behavioral symptoms of AD...
December 3, 2016: CNS Drugs
https://www.readbyqxmd.com/read/27913964/intracerebroventricular-streptozotocin-as-a-model-of-alzheimer-s-disease-neurochemical-and-behavioral-characterization-in-mice
#17
Katherine Garcia Ravelli, Barbara Dos Anjos Rosário, Rosana Camarini, Marina Sorrentino Hernandes, Luiz Roberto Britto
Streptozotocin has been widely used to mimic some aspects of Alzheimer's disease (AD). However, especially in mice, several characteristics involved in the streptozotocin (STZ)-induced AD pathology are not well known. The main purpose of this study was to evaluate temporally the expression of AD-related proteins, such as amyloid-β (Aβ), choline acetyltransferase (ChAT), synapsin, axonal neurofilaments, and phosphorylated Tau in the hippocampus following intracerebroventricular (icv) administration of STZ in adult mice...
December 2, 2016: Neurotoxicity Research
https://www.readbyqxmd.com/read/27913295/dissection-of-functional-lncrnas-in-alzheimer-s-disease-by-construction-and-analysis-of-lncrna-mrna-networks-based-on-competitive-endogenous-rnas
#18
Lian-Kun Wang, Xiao-Feng Chen, Dan-Dan He, You Li, Jin Fu
Alzheimer's disease (AD) is a neurodegenerative disorder that is the most common cause of dementia in the elderly, and intracellular neurofibrillary tangles (NFTs) are one of the pathological features of AD. Recent studies have suggested long noncoding RNAs (lncRNAs) play important roles in AD. Competing endogenous RNAs (ceRNAs) is a mechanism that has recently been proposed, in which lncRNAs compete for common miRNA-binding sites with mRNAs. However, the roles of lncRNAs and ceRNA in AD NFTs is limited. In this study, we constructed a global triple network based on ceRNA theory, then an AD NFT lncRNA-mRNA network (NFTLMN) was generated...
November 29, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27913252/sex-and-gender-differences-in-the-treatment-of-alzheimer-s-disease-a-systematic-review-of-randomized-controlled-trials
#19
Marco Canevelli, Federica Quarata, Francesca Remiddi, Flaminia Lucchini, Eleonora Lacorte, Nicola Vanacore, Giuseppe Bruno, Matteo Cesari
In recent years, epidemiological, clinical, and biological evidence has drawn the attention on the influence of sex and gender on Alzheimer's disease (AD). Nevertheless, not enough attention has been paid to their impact on treatment outcomes. The present study is aimed at systematically retrieve, review and discuss data coming from available randomized placebo-controlled trials (RCTs) on currently marketed treatments for AD (i.e., cholinesterase inhibitors [ChEIs] and memantine) in order to describe possible sex and gender differences in their efficacy, safety and tolerability...
November 30, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27913125/apomorphine-therapy-in-parkinson-s-and-future-directions
#20
Nataliya Titova, K Ray Chaudhuri
Apomorphine infusion or injection is an important dopamine agonist non-oral therapy usually used in advanced Parkinson's disease (PD) with refractory motor fluctuations. The drug also has appreciable efficacy for nonmotor fluctuations and is the quickest to reverse predictable "off" periods. Current subcutaneous administration, however, is complicated by problems associated with needle-based therapies, such as skin nodule formation, skin irritation, and avoidance of this treatment option by needle-phobic subjects...
November 30, 2016: Parkinsonism & related Disorders
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