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https://www.readbyqxmd.com/read/29232559/cilostazol-a-phosphodiesterase-3-inhibitor-activates-proteasome-proteolysis-and-attenuates-tauopathy-and-cognitive-decline
#1
Ari W Schaler, Natura Myeku
Alzheimer's disease and several variants of frontotemporal degeneration including progressive supranuclear palsy and corticobasal degeneration are characterized by the accumulation of abnormal tau protein into aggregates. Most proteins, including tau, are degraded via the ubiquitin proteasome system, but when abnormal tau accumulates, the function of 26S proteasomes is downregulated. The negative effect of tau aggregates on the function of the proteasome can have deleterious consequences on protein homeostasis and disease progression...
November 23, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29232315/beneficial-effects-of-exercise-pretreatment-in-a-sporadic-alzheimer-s-rat-model
#2
Chongyun Wu, Luodan Yang, Donovan Tucker, Yan Dong, Ling Zhu, Rui Duan, Timon Cheng-Yi Liu, Quanguang Zhang
PURPOSE: This study aimed to examine the effects of swimming exercise pretreatment on a streptozotocin (STZ)-induced sporadic Alzheimer's disease rat model and provide an initial understanding of related molecular mechanisms. METHODS: Male 2.5-month-old Sprague-Dawley rats were divided into the following 4 groups: a) control, b) swim + vehicle, c) STZ without swim, and d) swim + STZ. The Barnes Maze task and Novel Object Recognition test were used to measure hippocampus-dependent spatial learning and working memory, respectively...
December 11, 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/29232252/nicotinamide-adenine-dinucleotide-and-its-related-precursors-for-the-treatment-of-alzheimer-s-disease
#3
Nady Braidy, Ross Grant, Perminder S Sachdev
PURPOSE OF REVIEW: The current review discusses the biology and metabolism of the essential pyridine nucleotide nicotinamide adenine dinucleotide (NAD+) in the central nervous system. We also review recent work suggesting important neuroprotective effects that may be associated with the promotion of NAD+ levels through NAD+ precursors against Alzheimer's disease. RECENT FINDINGS: Perturbations in the physiological homoeostatic state of the brain during the ageing process can lead to impaired cellular function, and ultimately leads to loss of brain integrity and accelerates cognitive and memory decline...
December 9, 2017: Current Opinion in Psychiatry
https://www.readbyqxmd.com/read/29231506/-effects-and-mechanisms-of-different-frequencies-of-electroacupuncture-for-learning-and-memory-ability-of-alzheimer-s-rats
#4
Ying Wang, Lihong Kong, Wei Li, Kangkang Zhang, Feng Shen, Yawen Wang, Hua Zhou, Guojie Sun
OBJECTIVE: To observe the effects of different frequencies of electroacupuncture (EA) at "Baihui (GV 20)" and "Shenshu(BL 23)" for the learning and memory ability as well as glycogen synthase kinase-3β (GSK-3β) and growth associated protein-43 (GAP-43) in hippocampal tissue of rats with Alzheimer's disease(AD), so as to explore the mechanism of different frequencies of EA for the prevention and treatment of AD. METHODS: One hundred and twelve healthy Wistar male rats were divided into seven groups by random number table, namely a normal group, a sham operation group, a model group, an acupuncture group, a 2 Hz EA group, a 30 Hz EA group, and a 50 Hz EA group, 16 rats in each one...
June 12, 2017: Zhongguo Zhen Jiu, Chinese Acupuncture & Moxibustion
https://www.readbyqxmd.com/read/29231138/cholinesterase-inhibitor-6-chlorotacrine-in-vivo-toxicological-profile-and-behavioural-effects
#5
Jan Misik, Eugenie Nepovimova, Jaroslav Pejchal, Jiri Kassa, Jan Korabecny, Ondrej Soukup
BACKGROUND: 6-chlorotacrine is a cholinesterase inhibitor showing good inhibitory potential, even better than parent compound tacrine, in vitro. Despite tacrine scaffold is broadly used for design and synthesis of novel compounds with anti-Alzheimer's potential, no in vivo effects have been investigated so far. Thus, basic toxicological and behavioural evaluation has been carried out throughout this study. METHODS: Maximum tolerated dose (MTD) and median lethal dose (LD50) were assessed in BALB/c mice and Wistar rats...
December 11, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/29229355/effects-of-biflavonoids-from-garcinia-madruno-on-a-triple-transgenic-mouse-model-of-alzheimer-s-disease
#6
Angélica Maria Sabogal-Guáqueta, Luis Carrillo-Hormaza, Edison Osorio, Gloria Patricia Cardona-Gómez
Alzheimer's disease (AD) is a progressive neurodegenerative disorder that is pathologically characterized by the deposition of β-amyloid (βA) peptides in senile plaques and neurofibrillary tangles in the brain. Flavonoids have recently been used to prevent and treat a variety of neurodegenerative diseases, but little is known about bioflavonoids. In this study, we evaluate whether a biflavonoid fraction (BF) exerts neuroprotective effects on an aged triple transgenic mouse mode of AD (3xTg-AD). Then, 21-24-month-old 3xTg AD mice were i...
December 8, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29228318/microcystin-lr-induces-tau-pathology-through-b%C3%AE-degradation-via-pp2a-demethylation-and-associated-gsk-3%C3%AE-phosphorylation
#7
Yali Zhang, Jiahui Zhang, Enhao Wang, Wei Qian, Yan Fan, Ying Feng, Haimeng Yin, Yang Li, Yuning Wang, Tianli Yuan
Microcystin-LR (MC-LR) has been implicated as a potential environmental factor in Alzheimer's disease because of its potent inhibition of protein phosphatase 2A (PP2A) activity, but experimental evidence to support its detailed neurotoxic effects and their underlying mechanisms has been lacking. The present study investigated the role of PP2A catalytic subunit (PP2Ac) demethylation and its link with GSK-3β in tau hyperphosphorylation induced by MC-LR. The results showed that MC-LR treatment significantly increased demethylation of PP2Ac, with a concomitant increase in GSK-3β phosphorylation at Ser9 resulting in elevated tau hyperphosphorylation at PP2A-favorable sites in SH-SY5Y cells and rat hippocampus...
December 8, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29228074/a-review-of-the-current-therapies-challenges-and-future-directions-of-transcranial-focused-ultrasound-technology-advances-in-diagnosis-and-treatment
#8
Vibhor Krishna, Francesco Sammartino, Ali Rezai
Importance: Magnetic resonance imaging-guided focused ultrasound ablation has been approved for the treatment of refractory essential tremor and is being studied for other neurological indications, including dyskinesias and tremor in Parkinson disease, dystonia, neuropathic pain, obsessive-compulsive disorder, epilepsy, and brain tumors. Objective: To review the scientific foundations of FUS technology, existing neurological applications, and future advances. Evidence Review: PubMed was searched for the past 10 years using the terms "transcranial ultrasound," "focused ultrasound," and "neurological applications...
December 11, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/29228015/development-of-an-iron-selective-antioxidant-probe-with-protective-effects-on-neuronal-function
#9
Olimpo García-Beltrán, Natalia P Mena, Pabla Aguirre, Germán Barriga-González, Antonio Galdámez, Edgar Nagles, Tatiana Adasme, Cecilia Hidalgo, Marco T Núñez
Iron accumulation, oxidative stress and calcium signaling dysregulation are common pathognomonic signs of several neurodegenerative diseases, including Parkinson´s and Alzheimer's diseases, Friedreich ataxia and Huntington's disease. Given their therapeutic potential, the identification of multifunctional compounds that suppress these damaging features is highly desirable. Here, we report the synthesis and characterization of N-(1,3-dihydroxy-2-(hydroxymethyl)propan-2-yl)-2-(7-hydroxy-2-oxo-2H-chromen-4-yl)acetamide, named CT51, which exhibited potent free radical neutralizing activity both in vitro and in cells...
2017: PloS One
https://www.readbyqxmd.com/read/29226874/alterations-in-acrolein-metabolism-contribute-to-alzheimer-s-disease
#10
Han-Hsing Tsou, Wen-Chin Hsu, Jong-Ling Fuh, Shih-Pin Chen, Tsung-Yun Liu, Hsiang-Tsui Wang
Alzheimer's disease (AD) is a detrimental neurodegenerative disease, and early diagnosis appears to be the key to successful treatment. Acrolein, a byproduct of lipid peroxidation, has been shown to contribute to the pathological process of AD. This study recruited 118 elderly subjects consisting of 58 non-demented control subjects and 62 AD patients. We analyzed the acrolein-related metabolites in the plasma, cerebrospinal fluid (CSF), and urine of all subjects. We found that the levels of acrolein-conjugated protein (Acr-PC) in the plasma (p = 0...
December 1, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29226873/modeling-prion-like-processing-of%C3%A2-tau%C3%A2-protein-in-alzheimer-s-disease-for%C3%A2-pharmaceutical-development
#11
Claude M Wischik, Björn O Schelter, Damon J Wischik, John M D Storey, Charles R Harrington
 Following our discovery of a fragment from the repeat domain of tau protein as a structural constituent of the PHF-core in Alzheimer's disease (AD), we developed an assay that captured several key features of the aggregation process. Tau-tau binding through the core tau fragment could be blocked by the same diaminophenothiazines found to dissolve proteolytically stable PHFs isolated from AD brain. We found that the PHF-core tau fragment is inherently capable of auto-catalytic self-propagation in vitro, or "prion-like processing", that has now been demonstrated for several neurodegenerative disorders...
December 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29226868/predictors-of-age-of-diagnosis-and-survival-of-alzheimer-s-disease-in-down-syndrome
#12
Amanda Sinai, Claire Mokrysz, Jane Bernal, Ingrid Bohnen, Simon Bonell, Ken Courtenay, Karen Dodd, Dina Gazizova, Angela Hassiotis, Richard Hillier, Judith McBrien, Jane McCarthy, Kamalika Mukherji, Asim Naeem, Natalia Perez-Achiaga, Khadija Rantell, Vijaya Sharma, David Thomas, Zuzana Walker, Sarah Whitham, Andre Strydom
BACKGROUND: People with Down syndrome (DS) are an ultra-high risk population for Alzheimer's disease (AD). Understanding the factors associated with age of onset and survival in this population could highlight factors associated with modulation of the amyloid cascade. OBJECTIVE: This study aimed to establish the typical age at diagnosis and survival associated with AD in DS and the risk factors associated with these. METHODS: Data was obtained from the Aging with Down Syndrome and Intellectual Disabilities (ADSID) research database, consisting of data extracted from clinical records of patients seen by Community Intellectual Disability Services (CIDS) in England...
December 6, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29226862/the-rationale-and-design-of-the-reducing-pathology-in-alzheimer-s-disease-through-angiotensin-targeting-radar-trial
#13
Patrick G Kehoe, Peter S Blair, Beth Howden, David L Thomas, Ian B Malone, Jeremy Horwood, Clare Clement, Lucy Selman, Hannah Baber, Athene Lane, Elizabeth Coulthard, Anthony Peter Passmore, Nick C Fox, Ian B Wilkinson, Yoav Ben-Shlomo
BACKGROUND: Anti-hypertensives that modify the renin angiotensin system may reduce Alzheimer's disease (AD) pathology and reduce the rate of disease progression. OBJECTIVE: To conduct a phase II, two arm, double-blind, placebo-controlled, randomized trial (ISRCTN: 93682878; EudraCT: 2012-003641-15) of losartan to test the efficacy of Reducing pathology in Alzheimer's Disease through Angiotensin TaRgeting (RADAR). METHODS: Men and women aged at least 55 years with mild-to-moderate AD will be randomly allocated 100 mg encapsulated generic losartan or placebo once daily for 12 months after successful completion of a 2-week open-label phase and 2-week placebo washout to establish drug tolerability...
December 6, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29226720/memantine-induces-apoptosis-and-inhibits-cell-cycle-progression-in-lncap-prostate-cancer-cells
#14
G Albayrak, E Konac, A U Dikmen, C Y Bilen
Deregulated cancer cell metabolism plays an important role in cancer progression. Cancer cell metabolism has been in the centre of attention in therapeutical cancer cell targeting. Repurposed chemical agents, such as metformin and aspirin, have been studied extensively as preventive and therapeutic agents. Metformin is Food and Drug administration (FDA)-approved antidiabetic drug cheaper than other chemotherapeutic agents that were shown to have anticancer effects. Memantine is an FDA-approved Alzheimer's drug...
January 1, 2017: Human & Experimental Toxicology
https://www.readbyqxmd.com/read/29225190/scopolamine-induced-passive-avoidance-memory-retrieval-deficit-is-accompanied-with-hippocampal-mmp2-mmp-9-and-mapks-alteration
#15
Maryam Moosavi, Roksana SoukhakLari, Leila Moezi, Fatema Pirsalami
Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive loss of memory and cognitive deficit. The observed amnesia in the early stages of AD is suggested to be a retrieval problem, rather than encoding and consolidation deficit. According to the cholinergic hypothesis of AD, scopolamine is used to induce an animal model of amnesia. Howbeit the effect of scopolamine on memory retrieval is contradictory. This study aimed to assess the effect of scopolamine on passive avoidance memory retrieval...
December 7, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29225181/the-effect-of-green-synthesis-silver-nanoparticles-agnps-from-pulicaria-undulata-on-the-amyloid-formation-in-%C3%AE-lactalbumin-and-the-chaperon-action-of-%C3%AE-casein
#16
Mansoor Dehvari, Arezou Ghahghaei
The formation and deposition of protein fibrillar aggregates in the tissues is associated with several neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Molecular chaperones are a family of proteins that are believed to have the ability to inhibit protein aggregation. The present study examines the effect of different concentrations of green synthesis silver nanoparticles (AgNPs) from Pulicaria undulata L. on the aggregation of α-lactalbumin (α-LA) and the chaperone action of αs-casein...
December 7, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29225140/reactive-astrocytes-in-alzheimer-s-disease-a-double-edged-sword
#17
REVIEW
Heejung Chun, C Justin Lee
Alzheimer's disease (AD) is a chronic and fatal disease, in which neuronal damage at its late stage cannot be easily reversed. Because AD progression is caused by multiple factors including diverse cellular processes, studies on AD pathogenesis at the molecular and cellular level are challenging. Based on the lessons from unsuccessful neuron-focused research for an AD cure, non-cell autonomous mechanisms including brain inflammation and reactive astrocytes have recently been in the spotlight as potential therapeutic targets for AD...
December 7, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/29225107/comparison-of-blood-brain-barrier-penetration-efficiencies-between-linear-and-cyclic-all-d-enantiomeric-peptides-developed-for-the-treatment-of-alzheimer-s-disease
#18
Elena Schartmann, Sarah Schemmert, Tamar Ziehm, Leonie H E Leithold, Nan Jiang, Markus Tusche, N Jon Shah, Karl-Josef Langen, Janine Kutzsche, Dieter Willbold, Antje Willuweit
Alzheimer's disease (AD), until now, is an incurable progressive neurodegenerative disease. To target toxic amyloid β oligomers in AD patients' brains and to convert them into non-toxic aggregation-incompetent species, we designed peptides consisting solely of d-enantiomeric amino acid residues. The original lead compound was named D3 and several D3 derivatives were designed to enhance beneficial properties. Here, we compare four d-peptides concerning their efficiency to pass the blood-brain barrier (BBB)...
December 7, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29224179/antidiabetic-polypill-improves-central-pathology-and-cognitive-impairment-in-a-mixed-model-of-alzheimer-s-disease-and-type-2-diabetes
#19
Carmen Infante-Garcia, Juan Jose Ramos-Rodriguez, Carmen Hierro-Bujalance, Esperanza Ortegon, Eleanor Pickett, Rosemary Jackson, Fernando Hernandez-Pacho, Tara Spires-Jones, Monica Garcia-Alloza
Type 2 diabetes (T2D) is an important risk factor to suffer dementia, being Alzheimer's disease (AD) as the most common form. Both AD and T2D are closely related to aging and with a growing elderly population it might be of relevance to explore new therapeutic approaches that may slow or prevent central complications associated with metabolic disorders. Therefore, we propose the use of the antidiabetic polypill (PP), a pharmacological cocktail, commonly used by T2D patients that include metformin, aspirin, simvastatin, and an angiotensin-converting enzyme inhibitor...
December 9, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29223769/obstructive-sleep-apnoea-and-alzheimer-s-disease-in-search-of-shared-pathomechanisms
#20
REVIEW
D Polsek, N Gildeh, D Cash, R Winsky-Sommerer, S C R Williams, F Turkheimer, G D Leschziner, M J Morrell, I Rosenzweig
Alzheimer's disease (AD) is a significant public health concern. The incidence continues to rise, and it is set to be over one million in the UK by 2025. The processes involved in the pathogenesis of AD have been shown to overlap with those found in cognitive decline in patients with Obstructive Sleep Apnoea (OSA). Currently, the standard treatment for OSA is Continuous Positive Airway Pressure. Adherence to treatment can, however, be an issue, especially in patients with dementia. Also, not all patients respond adequately, necessitating the use of additional treatments...
December 6, 2017: Neuroscience and Biobehavioral Reviews
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