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Review of Alzheimer

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https://www.readbyqxmd.com/read/28823085/chromaffin-cells-as-a-model-to-evaluate-mechanisms-of-cell-death-and-neuroprotective-compounds
#1
REVIEW
Cristobal de Los Rios, Maria F Cano-Abad, Mercedes Villarroya, Manuela G López
In this review, we show how chromaffin cells have contributed to evaluate neuroprotective compounds with diverse mechanisms of action. Chromaffin cells are considered paraneurons, as they share many common features with neurons: (i) they synthesize, store, and release neurotransmitters upon stimulation and (ii) they express voltage-dependent calcium, sodium, and potassium channels, in addition to a wide variety of receptors. All these characteristics, together with the fact that primary cultures from bovine adrenal glands or chromaffin cells from the tumor pheochromocytoma cell line PC12 are easy to culture, make them an ideal model to study neurotoxic mechanisms and neuroprotective drugs...
August 19, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28822354/3d-brain-organoids-derived-from-pluripotent-stem-cells-promising-experimental-models-for-brain-development-and-neurodegenerative-disorders
#2
REVIEW
Chun-Ting Lee, Raphael M Bendriem, Wells W Wu, Rong-Fong Shen
Three-dimensional (3D) brain organoids derived from human pluripotent stem cells (hPSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), appear to recapitulate the brain's 3D cytoarchitectural arrangement and provide new opportunities to explore disease pathogenesis in the human brain. Human iPSC (hiPSC) reprogramming methods, combined with 3D brain organoid tools, may allow patient-derived organoids to serve as a preclinical platform to bridge the translational gap between animal models and human clinical trials...
August 20, 2017: Journal of Biomedical Science
https://www.readbyqxmd.com/read/28822176/-cerebral-microangiopathy-of-diabetes
#3
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/28821953/astrocyte-and-alzheimer-s-disease
#4
REVIEW
Zhiyou Cai, Cheng-Qun Wan, Zhou Liu
The past several decades have given rise to more insights into the role of astrocytes in normal brain function and diseases. Astrocytes elicit an effect which may be neuroprotective or deleterious in the process of Alzheimer's disease (AD). Impairments in astrocytes and their other functions, as well as physiological reactions of astrocytes to external injury, can trigger or exacerbate hyperphosphorylated tau and amyloid-beta (Aβ) pathologies, leading to the formation of both amyloid plaques and neurofibrillary tangles (NFTs), as well as neuronal dysfunction...
August 18, 2017: Journal of Neurology
https://www.readbyqxmd.com/read/28821400/alzheimer-s-disease-as-oligomeropathy
#5
REVIEW
Kenjiro Ono
Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder and is characterized by pathological aggregates of amyloid β-protein (Aβ) and tau protein. On the basis of genetic evidence, biochemical data, and animal models, Aβ has been suggested to be responsible for the pathogenesis of AD (the amyloid hypothesis). Aβ molecules tend to aggregate to form oligomers, protofibrils, and mature fibrils. Although mature fibrils in the final stage have been thought to be the cause of AD pathogenesis, recent studies using synthetic Aβ peptides, a cell culture model, Aβ precursor protein transgenic mice models, and human samples, such as cerebrospinal fluids and postmortem brains of AD patients, suggest that pre-fibrillar forms (oligomers of Aβ) are more deleterious than are extracellular fibril forms...
August 16, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28820437/are-astrocytes-the-predominant-cell-type-for-activation-of-nrf2-in-aging-and-neurodegeneration
#6
REVIEW
Jeffrey R Liddell
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates hundreds of antioxidant genes, and is activated in response to oxidative stress. Given that many neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease and multiple sclerosis are characterised by oxidative stress, Nrf2 is commonly activated in these diseases. Evidence demonstrates that Nrf2 activity is repressed in neurons in vitro, and only cultured astrocytes respond strongly to Nrf2 inducers, leading to the interpretation that Nrf2 signalling is largely restricted to astrocytes...
August 18, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/28820054/qsar-modeling-of-histamine-h3r-antagonists-inverse-agonists-as-future-drugs-for-neurodegenerative-diseases
#7
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/28819795/leptin-regulation-of-synaptic-function-at-hippocampal-ta-ca1-and-sc-ca1-synapses-implications-for-health-and-disease
#8
Gemma McGregor, Jenni Harvey
Growing evidence indicates that the endocrine hormone leptin regulates hippocampal synaptic function in addition to its established role as a hypothalamic satiety signal. Indeed, numerous studies show that leptin facilitates the cellular events that underlie hippocampal learning and memory including activity-dependent synaptic plasticity and glutamate receptor trafficking, indicating that leptin may be a potential cognitive enhancer. Although there has been extensive investigation into the modulatory role of leptin at hippocampal Schaffer collateral (SC)-CA1 synapses, recent evidence indicates that leptin also potently regulates excitatory synaptic transmission at the anatomically distinct temporoammonic (TA) input to hippocampal CA1 neurons...
August 18, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28818990/clinical-use-and-utility-of-amyloid-imaging
#9
Henryk Barthel, Osama Sabri
Currently, three amyloid PET tracers are approved and commercially available for clinical use. They allow for the accurate in vivo detection of amyloid plaques, one hallmark of Alzheimer's disease (AD). Here, we review the current knowledge on the clinical use and utility of amyloid imaging. Appropriate use criteria for the clinical application of amyloid imaging are established, and most currently available data point to their validity. Visual amyloid image analysis is highly standardized. Disclosure of amyloid imaging results is desired by many cognitively impaired subjects, and seems to be safe once appropriate education is delivered to the disclosing clinicians...
August 17, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28818091/non-canonical-soluble-amyloid-beta-aggregates-and-plaque-buffering-controversies-and-future-directions-for-target-discovery-in-alzheimer-s-disease
#10
REVIEW
David L Brody, Hao Jiang, Norelle Wildburger, Thomas J Esparza
The specific amyloid-beta (Aβ) species or other amyloid-precursor protein cleavage products that are most directly related to human neurodegeneration and clinical dementia of the Alzheimer's type have not yet been directly identified. Without a clear understanding of the most relevant species, it is difficult to determine whether therapeutic candidates successfully engaged the correct target(s). Here, we review some of the controversies regarding soluble Aβ aggregates (also termed oligomers, dimers, trimers, Aβ*56, amylospheroids, etc...
August 17, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28817967/pimavanserin-a-novel-antipsychotic-for-management-of-parkinson-s-disease-psychosis
#11
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/28817311/beta-secretase-inhibitors-in-phase-i-and-phase-ii-clinical-trials-for-alzheimer-s-disease
#12
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/28814397/association-of-tcn2-rs1801198-c-776g-c-polymorphism-with-markers-of-one-carbon-metabolism-and-related-diseases-a-systematic-review-and-meta-analysis-of-genetic-association-studies
#13
Abderrahim Oussalah, Julien Levy, Pierre Filhine-Trésarrieu, Fares Namour, Jean-Louis Guéant
Background: Vitamin B-12 (cobalamin) deficiency may produce severe neurologic and hematologic manifestations. Approximately 20-25% of circulating cobalamin binds to transcobalamin 2 (TCN2), which is referred to as active vitamin B-12. The G allele of the TCN2 c.776G>C (rs1801198) polymorphism has been associated with a lower plasma concentration of holotranscobalamin. However, genotype association studies on rs1801198 have led to conflicting results regarding its influence on one-carbon metabolism (OCM) markers or its association with pathologic conditions...
August 16, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28814391/filling-the-void-a-role-for-exercise-induced-bdnf-and-brain-amyloid-precursor-protein-processing
#14
Rebecca Ek MacPherson
Inactivity, obesity, and insulin resistance are significant risk factors for the development of Alzheimer's disease (AD). Several studies have demonstrated that diet induced obesity, inactivity, and insulin resistance exacerbates neuropathological hallmarks of AD. The aggregation of beta-amyloid peptides is one of these hallmarks. Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) is the rate-limiting enzyme in amyloid precursor protein (APP) processing, leading to beta-amyloid peptide formation...
August 16, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28814374/from-bench-laboratory-to-bed-hospital-home-how-to-explore-effective-natural-and-synthetic-pak1-blockers-longevity-promoters-for-cancer-therapy
#15
REVIEW
Hiroshi Maruta, Mok-Ryeon Ahn
PAK family kinases are RAC/CDC42-activated kinases that were first found in a soil amoeba 4 decades ago, and 2 decades later, were discovered in mammals as well. Since then at least 6 members of this family have been identified in mammals. One of them called PAK1 has been best studied so far, mainly because it is essential not only for malignant cell growth and metastasis, but also for many other diseases/disorders such as diabetes (type 2), AD (Alzheimer's disease), hypertension, and a variety of inflammatory or infectious diseases, which definitely shorten our lifespan...
August 9, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28814238/structural-insights-for-drugs-developed-for-phospholipase-d-enzymes
#16
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/28813734/the-36-hour-day-revisited-implementing-a-caregiver-support-system-into-primary-care-practice
#17
Rachel Sunne, Mark K Huntington
An estimated 5.3 million Americans had Alzheimer's disease in 2015. With the aging population and rapid rise in those with dementia, it is vital to not only care for the dementia patient, but also his or her primary caregiver. Caregivers often suffer from depression and neglect their own health in order to care for their loved one. In this regard, included is a review of the role of the primary care physician including the importance of discussing the diagnosis of dementia with the patient and family, providing supportive services and resources, as well as the challenges that many physicians face in tackling the care of a dementia caregiver...
April 2017: South Dakota Medicine: the Journal of the South Dakota State Medical Association
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
#18
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
https://www.readbyqxmd.com/read/28810002/retinal-oximetry-discovers-novel-biomarkers-in-retinal-and-brain-diseases
#19
Einar Stefánsson, Olof Birna Olafsdottir, Anna Bryndis Einarsdottir, Thorunn Scheving Eliasdottir, Thor Eysteinsson, Wouter Vehmeijer, Evelien Vandewalle, Toke Bek, Sveinn Hakon Hardarson
Purpose: Biomarkers for several eye and brain diseases are reviewed, where retinal oximetry may help confirm diagnosis or measure severity of disease. These include diabetic retinopathy, central retinal vein occlusion (CRVO), retinitis pigmentosa, glaucoma, and Alzheimer's disease. Methods: Retinal oximetry is based on spectrophotometric fundus imaging and measures oxygen saturation in retinal arterioles and venules in a noninvasive, quick, safe manner. Retinal oximetry detects changes in oxygen metabolism, including those that result from ischemia or atrophy...
May 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28809653/effectiveness-of-environment-based-interventions-that-address-behavior-perception-and-falls-in-people-with-alzheimer-s-disease-and-related-major-neurocognitive-disorders-a-systematic-review
#20
Lou Jensen, René Padilla
OBJECTIVE: This systematic review evaluated the effectiveness of environment-based interventions that address behavior, perception, and falls in the home and other settings for people with Alzheimer's disease (AD) and related major neurocognitive disorders (NCDs). METHOD: Database searches were limited to outcomes studies published in English in peer-reviewed journals between January 2006 and April 2014. RESULTS: A total of 1,854 articles were initially identified, of which 42 met inclusion criteria...
September 2017: American Journal of Occupational Therapy: Official Publication of the American Occupational Therapy Association
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