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https://www.readbyqxmd.com/read/28822176/-cerebral-microangiopathy-of-diabetes
#1
REVIEW
Yuan Li, Ke-Wu Zeng, Xue-Mei Wang
Diabetes mellitus, a kind of chronic metabolic disease, has become one of major threats to human health with an increasing incidence. As a basic pathology of chronic complications related to diabetes mellitus, cerebral microangiopathy is mainly found in patients with Alzheimer's disease and lacunar infarction, and becomes one of the main reasons of death and disability in diabetic patients. The pathogenesis of cerebral microangiopathy is complicated, involving such signal pathways as metabolic abnormalities of polyol, saccharification hyperactivity, oxidative stress, abnormal transport of amyloid-β across blood-brain barrier and protein kinase C activation...
June 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/28821686/effect-of-simvastatin-on-csf-alzheimer-disease-biomarkers-in-cognitively-normal-adults
#2
Ge Li, Cynthia L Mayer, Daniel Morelli, Steven P Millard, Wendy H Raskind, Eric C Petrie, Monique Cherrier, Anne M Fagan, Murray A Raskind, Elaine R Peskind
OBJECTIVE: To examine potential disease-modifying effects of statin drugs, we conducted a 12-month randomized, placebo-controlled clinical trial of simvastatin in cognitively normal adults using change in CSF Alzheimer disease biomarkers as primary outcome measure. METHODS: Participants were 45-64 years old and statin-naive with normal cognition and normal or mildly elevated cholesterol. Forty-six participants completed the 1-year study per protocol (25 in the simvastatin and 21 in the placebo group)...
August 18, 2017: Neurology
https://www.readbyqxmd.com/read/28821008/trans-caryophyllene-inhibits-amyloid-%C3%AE-a%C3%AE-oligomer-induced-neuroinflammation-in-bv-2-microglial-cells
#3
Yawei Hu, Ziling Zeng, Baojie Wang, Shougang Guo
Amyloid β (Aβ) is the major component of senile plaques (SP) in the brains of Alzheimer's disease (AD) patients, and serves as an inflammatory stimulus for microglia. Trans-caryophyllene (TC), a major component in the essential oils derived from various species of medicinal plants, has displayed its neuro-protective effects in previous studies. However, whether TC has a protective role in AD remains unknown. In this study, the effects of TC on Aβ1-42-induced neuro-inflammation were investigated. We found that TC reduced the release of LDH in BV-2 microglial cells treated with Aβ1-42...
August 15, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28820054/qsar-modeling-of-histamine-h3r-antagonists-inverse-agonists-as-future-drugs-for-neurodegenerative-diseases
#4
Michelle Fidelis Corrêa, João Paulo Dos Santos Fernandes
Histamine H3 receptor (H3R) is associated with several neuropsychological diseases. It is predominantly expressed in the central nervous system as presynaptic receptor, especially in regions associated with cognition and behavior, and is responsible for modulate the synthesis and release of histamine and other neurotransmitters such as acetylcholine, dopamine and serotonin. Therefore, H3R is an important target involved in several CNS disorders, such as narcolepsy, attention deficit hyperactivity disorder and schizophrenia...
August 17, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28819903/inhibition-of-pten-attenuates-endoplasmic-reticulum-stress-and-apoptosis-via-activation-of-pi3k-akt-pathway-in-alzheimer-s-disease
#5
Weigang Cui, Songtao Wang, Zhongping Wang, Zhiyong Wang, Chunli Sun, Yinghua Zhang
Amyloid plaques and neurofibrillary tangles are pathologic hallmarks of Alzheimer's disease (AD). Endoplasmic reticulum (ER) stress has been implicated in the loss of neurons in AD. The phosphatase and tensin homolog deleted on chromosome ten (PTEN) plays an important role in regulating neuronal survival processes. However, the direct effects of the PTEN on ER stress and apoptosis in AD have not been elucidated. In this study, we demonstrate that the expression of PTEN and ER stress related proteins, GRP78 and CHOP, increased in APP/PS1 transgenic AD mice compared with WT mice...
August 18, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28818766/design-synthesis-and-in%C3%A2-vivo-study-of-novel-pyrrolidine-based-11%C3%AE-hsd1-inhibitors-for-age-related-cognitive-dysfunction
#6
Rosana Leiva, Christian Griñan-Ferré, Constantí Seira, Elena Valverde, Andrew McBride, Margaret Binnie, Belén Pérez, F Javier Luque, Mercè Pallàs, Axel Bidon-Chanal, Scott P Webster, Santiago Vázquez
Recent findings suggest that treatment with 11β-HSD1 inhibitors provides a novel approach to deal with age-related cognitive dysfunctions, including Alzheimer's disease. In this work we report potent 11β-HSD1 inhibitors featuring unexplored pyrrolidine-based polycyclic substituents. A selected candidate administered to 12-month-old SAMP8 mice for four weeks prevented memory deficits and displayed a neuroprotective action. This is the first time that 11β-HSD1 inhibitors have been studied in this broadly-used mouse model of accelerated senescence and late-onset Alzheimer's disease...
August 4, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28818116/distinct-white-matter-microstructural-abnormalities-and-extracellular-water-increases-relate-to-cognitive-impairment-in-alzheimer-s-disease-with-and-without-cerebrovascular-disease
#7
Fang Ji, Ofer Pasternak, Siwei Liu, Yng Miin Loke, Boon Linn Choo, Saima Hilal, Xin Xu, Mohammad Kamran Ikram, Narayanaswamy Venketasubramanian, Christopher Li-Hsian Chen, Juan Zhou
BACKGROUND: Mixed vascular and neurodegenerative dementia, such as Alzheimer's disease (AD) with concomitant cerebrovascular disease, has emerged as the leading cause of age-related cognitive impairment. The brain white matter (WM) microstructural changes in neurodegeneration well-documented by diffusion tensor imaging (DTI) can originate from brain tissue or extracellular free water changes. The differential microstructural and free water changes in AD with and without cerebrovascular disease, especially in normal-appearing WM, remain largely unknown...
August 17, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28817967/pimavanserin-a-novel-antipsychotic-for-management-of-parkinson-s-disease-psychosis
#8
Yasaman Kianirad, Tanya Simuni
Parkinson's disease psychosis (PDP) may develop in up to 60% of Parkinson's patients and is associated with increased morbidity and mortality. It also correlates with depression and dementia, and can contribute to caregiver stress and burnout. Pimavanserin is the first FDA approved drug for the treatment of hallucinations and delusions associated with PDP. Areas covered: For this review, a MEDLINE literature search (via PubMed) and information provided by ACADIA Pharmaceuticals were used. References of our search results were screened for additional studies...
August 18, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28817841/-practical-use-of-continuous-apomorphine-infusion-via-pump
#9
Lars Tönges, Andrés Ceballos-Baumann, Holger Honig, Alexander Storch, Wolfgang H Jost
Parkinson's disease is the second most common neurodegenerative illness after Alzheimer's disease. In its advanced stages, it is characterized by various special symptoms. In addition to non-motor signs, motor complications are most prominent and most often can only be inadequately improved with pulsatile oral therapies. However, with the aid of continuous dopaminergic stimulation, improvements can be achieved even in advanced stages of the disease. This will not only alleviate motor and non-motor symptoms, but will also lead to a better quality of life...
August 17, 2017: Fortschritte der Neurologie-Psychiatrie
https://www.readbyqxmd.com/read/28817311/beta-secretase-inhibitors-in-phase-i-and-phase-ii-clinical-trials-for-alzheimer-s-disease
#10
Charbel E-H Moussa
BACE 1 is a protease that cleaves the transmembrane amyloid precursor protein and generates amyloid-β peptides that accumulate in AD brains. No known mutations are identified in the gene encoding BACE1 in AD. However, enzyme levels are elevated in AD and a single residue mutation in amyloid precursor protein protects against protein cleavage by BACE1, suggesting BACE involvement in disease pathogenesis. Drugs that can inhibit BACE1 would theoretically prevent Aβ accumulation and halt AD onset and progression...
August 17, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28817274/notch-inhibitors-from-calotropis-gigantea-that-induce-neuronal-differentiation-of-neural-stem-cells
#11
Tatsuro Yoneyama, Midori A Arai, Ryuta Akamine, Kazune Koryudzu, Anna Tsuchiya, Samir K Sadhu, Firoj Ahmed, Motoyuki Itoh, Ryuichi Okamoto, Masami Ishibashi
Neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease occur due to loss of the structure and function of neurons. For the potential treatment of neurodegenerative diseases, accelerators of neuronal differentiation of neural stem cells (NSCs) have been focused on and a cell-based assay system for measuring Notch signaling pathway activity was constructed. Using this assay system, eight compounds isolated from Calotropis gigantea were identified as inhibitors of the Notch signaling pathway...
August 17, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28817221/neuroprotective-effects-of-honokiol-from-chemistry-to-medicine
#12
REVIEW
Sylwia Talarek, Joanna Listos, Davide Barreca, Ester Tellone, Antoni Sureda, Seyed Fazel Nabavi, Nady Braidy, Seyed Mohammad Nabavi
The incidence of neurological disorders is growing in developed countries together with increased lifespan. Nowadays, there are still no effective treatments for neurodegenerative pathologies, which make necessary to search for new therapeutic agents. Natural products, most of them used in traditional medicine, are considered promising alternatives for the treatment of neurodegenerative diseases. Honokiol is a natural bioactive phenylpropanoid compound, belonging to the class of neolignan, found in notable amounts in the bark of Magnolia tree, and has been reported to exert diverse pharmacological properties including neuroprotective activities...
August 17, 2017: BioFactors
https://www.readbyqxmd.com/read/28816008/lactuca-capensis-reverses-memory-deficits-in-a%C3%AE-1-42-induced-an-animal-model-of-alzheimer-s-disease
#13
Paula Alexandra Postu, Jaures A K Noumedem, Oana Cioanca, Monica Hancianu, Marius Mihasan, Mitica Ciorpac, Dragos Lucian Gorgan, Brindusa Alina Petre, Lucian Hritcu
We investigated the neuropharmacological effects of the methanolic extract from Lactuca capensis Thunb. leaves (100 and 200 mg/kg) for 21 days on memory impairment in an Alzheimer's disease (AD) rat model produced by direct intraventricular delivery of amyloid-β1-42 (Aβ1-42). Behavioural assays such as Y-maze and radial arm maze test were used for assessing memory performance. Aβ1-42 decreased cognitive performance in the behavioural tests which were ameliorated by pre-treatment with the methanolic extract...
August 16, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28815739/kernicterus-in-a-boy-with-ornithine-transcarbamylase-deficiency-a-case-report
#14
Eduardo López-Corella, Isabel Ibarra-González, Cynthia Fernández-Lainez, Miguel Á Rodríguez-Weber, Sara Guillén-Lopez, Leticia Belmont-Martínez, David Agüero-Linares, Marcela Vela-Amieva
Ornithine transcarbamylase deficiency (OTCD) is an X-linked urea cycle defect associated with severe and usually fatal hyperammonemia. This study describes a patient with early onset lethal OTCD due to a known pathogenic variant (c.298+1G>A), as well as the novel autopsy finding of kernicterus with relatively low blood concentration of unconjugated bilirubin (UCB) (11.55 mg/dL). The patient was a full-term male with a family history of two previous male siblings who died as newborns after acute neurologic deterioration...
August 16, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/28815614/resveratrol-for-alzheimer-s-disease
#15
REVIEW
Christine Sawda, Charbel Moussa, R Scott Turner
The amyloid hypothesis suggests that the progressive accumulation and deposition of central nervous system (CNS) amyloid with aging is the proximate cause of Alzheimer's disease (AD). Thus, targeting molecular mechanisms of aging may be a viable treatment approach. Caloric restriction prevents diseases of aging, including AD, in animal models, perhaps by activation of sirtuins. The sirtuins (e.g., mammalian SIRT1) are deacetylases that link energy balance (NAD(+) /NADH) to regulation of gene transcription. Resveratrol is a potent activator of SIRT1, and thus may mimic caloric restriction to prevent diseases of aging...
August 16, 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28815510/inhibition-of-%C3%AE-secretase-leads-to-an-increase-in-presenilin-1
#16
Aitana Sogorb-Esteve, María-Salud García-Ayllón, Marta Llansola, Vicente Felipo, Kaj Blennow, Javier Sáez-Valero
γ-Secretase inhibitors (GSIs) are potential therapeutic agents for Alzheimer's disease (AD); however, trials have proven disappointing. We addressed the possibility that γ-secretase inhibition can provoke a rebound effect, elevating the levels of the catalytic γ-secretase subunit, presenilin-1 (PS1). Acute treatment of SH-SY5Y cells with the GSI LY-374973 (N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester, DAPT) augments PS1, in parallel with increases in other γ-secretase subunits nicastrin, presenilin enhancer 2, and anterior pharynx-defective 1, yet with no increase in messenger RNA expression...
August 16, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28814238/structural-insights-for-drugs-developed-for-phospholipase-d-enzymes
#17
Kimberly Stieglitz
BACKGROUND: In recent years human phospholipase D enzymes (PLD1 and PLD2 isozymes) have emerged as drug targets for various diseases such as cardiovascular disease, cancer, infectious diseases and neurodegenerative conditions such as Alzheimer's and Parkinson's disease. The interest in PLD as a drug target is due to the fact that PLD enzymes belong to a superfamily of phospholipases that are essential to intracellular and extracellular signaling. Many bioactive lipid signaling molecules are generated by these enzymes including phosphatidic and lysophosphatidic acid, arachidonic acid, and diacylglycerol (DAG)...
August 15, 2017: Current Drug Discovery Technologies
https://www.readbyqxmd.com/read/28812474/protective-effect-of-raisin-currant-against-spatial-memory-impairment-and-oxidative-stress-in-alzheimer-disease-model
#18
Mohammad Gol, Davoud Ghorbanian, Nabiollah Soltanpour, Jamshid Faraji, Mohsen Pourghasem
OBJECTIVES: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive pathological changes of the brain. A number of studies demonstrated compelling evidence of the importance of oxidative processes in AD pathogenesis. Raisin contains polyphenol, phenolic acid, and tannin compounds, which have antioxidant and anti-inflammatory properties. The present study was aimed to evaluate the protective effect of raisin on neurobehavioral and histological changes in rats with Alzheimer...
August 16, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/28812049/importance-of-adiponectin-activity-in-the-pathogenesis-of-alzheimer-s-disease
#19
REVIEW
Masaaki Waragai, Gilbert Ho, Yoshiki Takamatsu, Kazunari Sekiyama, Shuei Sugama, Takato Takenouchi, Eliezer Masliah, Makoto Hashimoto
A recent study suggested that insulin resistance may play a central role in the pathogenesis of Alzheimer's disease (AD). In this regard, it is of note that upregulation of plasma adiponectin (APN), a benign adipokine that sensitizes the insulin receptor signaling pathway and suppresses inflammation, has recently been associated with the severities of amyloid deposits and cognitive deficits in the elderly, suggesting that APN may enhance the risk of AD. These results are unanticipated because AD has been linked to type II diabetes and other metabolic disorders in which hypoadiponectinemia has been firmly established, and because APN ameliorated neuropathological features in a mouse model of neurodegeneration...
August 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28811745/inhibition-of-inflammation-mediated-through-the-tumor-necrosis-factor-%C3%AE-biochemical-pathway-can-lead-to-favorable-outcomes-in-alzheimer-disease
#20
REVIEW
Daniah Shamim, Michael Laskowski
Tumor necrosis factor α (TNF-α) inhibitors have long been used as disease-modifying agents in immune disorders. Recently, research has shown a role of chronic neuroinflammation in the pathophysiology of neurodegenerative diseases such as Alzheimer disease, and interest has been generated in the use of anti-TNF agents and TNF-modulating agents for prevention and treatment. This article extensively reviewed literature on animal studies testing these agents. The results showed a role for direct and indirect TNF-α inhibition through agents such as thalidomide, 3,6-dithiothalidomide, etanercept, infliximab, exendin-4, sodium hydrosulfide, minocycline, imipramine, and atorvastatin...
2017: Journal of Central Nervous System Disease
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