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https://www.readbyqxmd.com/read/28229638/intranasal-insulin-treatment-improves-memory-and-learning-in-a-rat-amyloid-beta-model-of-alzheimer-s-disease
#1
S Farzampour, A Majdi, S Sadigh-Eteghad
Recently, insulin has been used as a pro-cognitive agent for the potential treatment of Alzheimer's disease (AD), because of its ability to cross the brain-blood barrier (BBB) by a saturable transport system. This study has been designed to evaluate the effects of intranasal insulin regimen, as a bypass system of BBB, on spatial memory in amyloid-beta (Aβ) model of AD in rat. Unilateral infusion of Aβ25-35 (10 nmol/2 µl/rat) into the lateral ventricular region of brain was used to produce a rat model of AD...
September 2016: Physiol Int
https://www.readbyqxmd.com/read/28228714/narrative-organization-deficit-in-lewy-body-disorders-is-related-to-alzheimer-pathology
#2
Murray Grossman, David J Irwin, Charles Jester, Amy Halpin, Sharon Ash, Katya Rascovsky, Daniel Weintraub, Corey T McMillan
Background: Day-to-day interactions depend on conversational narrative, and we examine here the neurobiological basis for difficulty organizing narrative discourse in patients with Lewy body disorders (LBD). Method: Narrative organization was examined in 56 non-aphasic LBD patients, including a non-demented cohort (n = 30) with Parkinson's disease (PD) or PD-Mild Cognitive Impairment PD-MCI,) and a cohort with mild dementia (n = 26) including PD-dementia (PDD) and dementia with Lewy bodies (DLB), with similar age and education but differing in MMSE (p < 0...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28228553/the-novel-mitochondrial-matrix-protease-ste23-is-required-for-efficient-presequence-degradation-and-processing
#3
Asli Aras Taskin, Cansu Kücükköse, Nils Burger, Dirk Mossmann, Chris Meisinger, F-Nora Vögtle
Around 70% of mitochondrial precursor proteins are imported from the cytosol via N-terminal presequences, which are cleaved upon exposure to the mitochondrial processing protease MPP in the matrix. Cleaved presequence peptides then need to be efficiently degraded and impairment of this clearance step e.g. by amyloid beta peptides causes a feedback inhibition of MPP leading ultimately to accumulation of immature precursor proteins within mitochondria. Degradation of mitochondrial peptides is performed by Cym1 in yeast and its homolog PreP in humans...
February 22, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28223932/cerebrospinal-fluid-levels-of-amyloid-beta-1-43-mirror-1-42-in-relation-to-imaging-biomarkers-of-alzheimer-s-disease
#4
Ina S Almdahl, Camilla Lauridsen, Per Selnes, Lisa F Kalheim, Christopher Coello, Beata Gajdzik, Ina Møller, Marianne Wettergreen, Ramune Grambaite, Atle Bjørnerud, Geir Bråthen, Sigrid B Sando, Linda R White, Tormod Fladby
Introduction: Amyloid beta 1-43 (Aβ43), with its additional C-terminal threonine residue, is hypothesized to play a role in early Alzheimer's disease pathology possibly different from that of amyloid beta 1-42 (Aβ42). Cerebrospinal fluid (CSF) Aβ43 has been suggested as a potential novel biomarker for predicting conversion from mild cognitive impairment (MCI) to dementia in Alzheimer's disease. However, the relationship between CSF Aβ43 and established imaging biomarkers of Alzheimer's disease has never been assessed...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28223920/therapeutic-potential-of-secreted-amyloid-precursor-protein-apps%C3%AE
#5
REVIEW
Bruce G Mockett, Max Richter, Wickliffe C Abraham, Ulrike C Müller
Cleavage of the amyloid precursor protein (APP) by α-secretase generates an extracellularly released fragment termed secreted APP-alpha (APPsα). Not only is this process of interest due to the cleavage of APP within the amyloid-beta sequence, but APPsα itself has many physiological properties that suggest its great potential as a therapeutic target. For example, APPsα is neurotrophic, neuroprotective, neurogenic, a stimulator of protein synthesis and gene expression, and enhances long-term potentiation (LTP) and memory...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28220046/osmotin-reduced-amyloid-beta-a%C3%AE-burden-by-inhibiting-srebp2-expression-in-app-ps1-mice
#6
S A Shah, G H Yoon, S S Chung, M N Abid, T H Kim, H Y Lee, M O Kim
No abstract text is available yet for this article.
February 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28215000/angiotensin-ii-receptor-blockers-attenuate-lipopolysaccharide-induced-memory-impairment-by-modulation-of-nf-%C3%AE%C2%BAb-mediated-bdnf-creb-expression-and-apoptosis-in-spontaneously-hypertensive-rats
#7
Ruby Goel, Shahnawaz Ali Bhat, Kashif Hanif, Chandishwar Nath, Rakesh Shukla
Clinical studies demonstrated a positive correlation between hypertension and cognitive decline. Beneficial effects of angiotensin II receptor blockers on cognitive functions have also been reported earlier; however, its role in chronic neuroinflammation-induced memory impairment in the hypertensive state is not well understood. Therefore, in the present study, we investigated the effect of angiotensin II receptor blockers on memory impairment induced by lipopolysaccharide (LPS) in spontaneously hypertensive rats (SHRs)...
February 18, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28213109/screening-of-plants-used-in-the-european-traditional-medicine-to-treat-memory-disorders-for-acetylcholinesterase-inhibitory-activity-and-anti-amyloidogenic-activity
#8
Eva S Lobbens, Karina J Vissing, Lene Jorgensen, Marco van de Weert, Anna K Jäger
ETHNOPHARMACOLOGICAL RELEVANCE: Plants used in the traditional medicine of Europe to treat memory dysfunction and/or to enhance memory were investigated for activity against the underlying mechanisms of Alzheimer's disease. AIM OF THE STUDY: To investigate 35 ethanolic extracts of plants, selected using an ethnopharmacological approach, for anti-amyloidogenic activity as well as an ability to inhibit the enzymatic activity of acetylcholinesterase. MATERIALS AND METHODS: The anti-amyloidogenic activity of the extracts against amyloid beta was investigated by Thioflavin T fibrillation assays and the ability to inhibit the enzymatic activity of acetylcholinesterase was evaluated monitoring the hydrolysis of acetylthiocholine RESULTS: Under the experimental conditions investigated, extracts of two plants, Carum carvi and Olea sylvestris, inhibited amyloid beta fibrillation considerably, eight plant extracts inhibited amyloid beta fibrillation to some extent, 16 plant extracts had no effect on amyloid beta fibrillation and nine extracts accelerated fibrillation of amyloid beta...
February 14, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28211900/amyloid-%C3%AE-oligomers-interact-with-neurexin-and-diminish-neurexin-mediated-excitatory-presynaptic-organization
#9
Yusuke Naito, Yuko Tanabe, Alfred Kihoon Lee, Edith Hamel, Hideto Takahashi
Alzheimer's disease (AD) is characterized by excessive production and deposition of amyloid-beta (Aβ) proteins as well as synapse dysfunction and loss. While soluble Aβ oligomers (AβOs) have deleterious effects on synapse function and reduce synapse number, the underlying molecular mechanisms are not well understood. Here we screened synaptic organizer proteins for cell-surface interaction with AβOs and identified a novel interaction between neurexins (NRXs) and AβOs. AβOs bind to NRXs via the N-terminal histidine-rich domain (HRD) of β-NRX1/2/3 and alternatively-spliced inserts at splicing site 4 of NRX1/2...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28211008/injected-amyloid-beta-in-the-olfactory-bulb-transfers-to-other-brain-regions-via-neural-connections-in-mice
#10
Baixuan He, Minying Zheng, Qiang Liu, Zhe Shi, Simei Long, Xilin Lu, Zhong Pei, Ti-Fei Yuan, Huanxing Su, Xiaoli Yao
Alzheimer's disease (AD) is characterized by progressive neuronal degeneration and pathological accumulation of amyloid plaques in the brain. It has been proposed that the prion-like spreading of amyloid beta (Aβ) protein could contribute to the progression of the disease. Olfactory bulb (OB) is one of the earliest brain regions affected in AD and olfaction is easily impaired prior to cognitive symptoms. However, it remains unclear whether Aβ accumulation in the OB would spread along olfactory projections to other connected brain regions and trigger further neurodegeneration...
February 16, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28210222/icariside-ii-a-broad-spectrum-anti-cancer-agent-reverses-beta-amyloid-induced-cognitive-impairment-through-reducing-inflammation-and-apoptosis-in-rats
#11
Yuanyuan Deng, Long Long, Keke Wang, Jiayin Zhou, Lingrong Zeng, Lianzi He, Qihai Gong
Beta-amyloid (Aβ) deposition, associated neuronal apoptosis and neuroinflammation are considered as the important factors which lead to cognitive deficits in Alzheimer's disease (AD). Icariside II (ICS II), an active flavonoid compound derived from Epimedium brevicornum Maxim, has been extensively used to treat erectile dysfunction, osteoporosis and dementia in traditional Chinese medicine. Recently, ICS II attracts great interest due to its broad-spectrum anti-cancer property. ICS II shows an anti-inflammatory potential both in cancer treatment and cerebral ischemia-reperfusion...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28205591/protective-effect-of-17%C3%AE-estradiol-upon-hippocampal-spine-density-and-cognitive-function-in-an-animal-model-of-vascular-dementia
#12
Ying Zhu, Quanguang Zhang, Wenli Zhang, Ning Li, Yongxin Dai, Jingyi Tu, Fang Yang, Darrell W Brann, Ruimin Wang
The current study examined whether the steroid hormone, 17β-estradiol (E2) can exert long-lasting beneficial effects upon axonal health, synaptic plasticity, dementia-related amyloid-beta (Aβ) protein expression, and hippocampal-dependent cognitive function in an animal model of chronic cerebral hypoperfusion and vascular dementia (VaD). Chronic cerebral hypoperfusion and VaD was induced by bilateral common carotid artery occlusion (BCCAO) in adult male Sprague Dawley rats. Low dose E2 administered for the first 3-months after BCCAO exerted long-lasting beneficial effects, including significant neuroprotection of hippocampal CA1 neurons and preservation of hippocampal-dependent cognitive function when examined at 6-months after BCCAO...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28197076/structure-and-synaptic-function-of-metal-binding-to-the-amyloid-precursor-protein-and-its-proteolytic-fragments
#13
REVIEW
Klemens Wild, Alexander August, Claus U Pietrzik, Stefan Kins
Alzheimer's disease (AD) is ultimately linked to the amyloid precursor protein (APP). However, current research reveals an important synaptic function of APP and APP-like proteins (APLP1 and 2). In this context various neurotrophic and neuroprotective functions have been reported for the APP proteolytic fragments sAPPα, sAPPβ and the monomeric amyloid-beta peptide (Aβ). APP is a metalloprotein and binds copper and zinc ions. Synaptic activity correlates with a release of these ions into the synaptic cleft and dysregulation of their homeostasis is linked to different neurodegenerative diseases...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28193522/intracerebroventricular-injection-of-beta-amyloid-in-mice-is-associated-with-long-term-cognitive-impairment-in-the-modified-hole-board-test
#14
Sebastian Schmid, Bettina Jungwirth, Verena Gehlert, Manfred Blobner, Gerhard Schneider, Stephan Kratzer, Kristine Kellermann, Gerhard Rammes
BACKGROUND: The intracerebroventricular injection of beta-amyloid (Aβ) in mice allows the investigation of acute effects on cognitive function and cellular pathology. The aim of this investigation was to further characterize the time course of Aβ-induced cognitive and behavioural changes and to detect potential molecular mechanisms. METHODS: Cannulas were implanted in the lateral cerebral ventricle. 14days after surgery the mice were injected with Aβ1-42 or phosphate buffered saline (PBS)...
February 10, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28190529/mitophagy-and-alzheimer-s-disease-cellular-and-molecular-mechanisms
#15
REVIEW
Jesse S Kerr, Bryan A Adriaanse, Nigel H Greig, Mark P Mattson, M Zameel Cader, Vilhelm A Bohr, Evandro F Fang
Neurons affected in Alzheimer's disease (AD) experience mitochondrial dysfunction and a bioenergetic deficit that occurs early and promotes the disease-defining amyloid beta peptide (Aβ) and Tau pathologies. Emerging findings suggest that the autophagy/lysosome pathway that removes damaged mitochondria (mitophagy) is also compromised in AD, resulting in the accumulation of dysfunctional mitochondria. Results in animal and cellular models of AD and in patients with sporadic late-onset AD suggest that impaired mitophagy contributes to synaptic dysfunction and cognitive deficits by triggering Aβ and Tau accumulation through increases in oxidative damage and cellular energy deficits; these, in turn, impair mitophagy...
February 9, 2017: Trends in Neurosciences
https://www.readbyqxmd.com/read/28188785/sortilin-related-receptor-1-interacts-with-amyloid-precursor-protein-and-is-activated-by-6-shogaol-leading-to-inhibition-of-the-amyloidogenic-pathway
#16
Ji-Young Na, Kibbeum Song, Ju-Woon Lee, Sokho Kim, Jungkee Kwon
Sortilin-related receptor 1 (SORL1) is a neuronal sorting protein that reduces amyloid precursor protein (APP) trafficking to secretases that generate amyloid beta (Aβ). Although 6-shogaol, a constituent of ginger, has been reported to have anti-inflammatory and anti-oxidant effects on neuronal cells, research regarding the activation of SORL1 has not yet been reported. Here, we aimed to investigate whether 6-shogaol contributes to the increases in SORL1 that are related to Alzheimer's disease (AD). To clarify the effect of 6-shogaol as a possible activator of SORL1, we used SORL1 siRNA as a blockade of SORL1 in hippocampal neuronal cells (HT22)...
February 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28188358/protective-effect-of-valproic-acid-in-streptozotocin-induced-sporadic-alzheimer-s-disease-mouse-model-possible-involvement-of-the-cholinergic-system
#17
Mirna Ezzat Sorial, Nesrine Salah El Dine El Sayed
Sporadic Alzheimer's disease (SAD) is a slowly progressive neurological disorder that is the most common form of dementia. Cholinergic system dysfunction and amyloid beta formation are the two main underlying pathological mechanisms for the disease development. In recent studies, insulin receptor desensitization and disturbances in the downstream effects of insulin receptor signaling were observed in the brains of Alzheimer's patients. Currently, intracereberoventricular (ICV) injection of streptozotocin (STZ) is found to induce behavioral, neurochemical, and structural alterations in animals resembling those found in SAD patients...
February 10, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28188218/focal-solute-trapping-and-global-glymphatic-pathway-impairment-in-a-murine-model-of-multiple-microinfarcts
#18
Minghuan Wang, Fengfei Ding, SaiYue Deng, Xuequn Guo, Wei Wang, Jeffrey J Iliff, Maiken Nedergaard
Microinfarcts occur commonly in the aging brain as a consequence of diffuse embolic events and are associated with the development of vascular dementia and Alzheimer's disease. Yet the manner in which disperse microscopic lesions reduce global cognitive function and increase the risk for Alzheimer's disease is unclear. The glymphatic system, which is a brain-wide perivascular network that supports the recirculation of CSF through the brain parenchyma, facilitates the clearance of interstitial solutes including amyloid beta and tau...
February 10, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28185874/psychosocial-stress-on-neuroinflammation-and-cognitive-dysfunctions-in-alzheimer-s-disease-the-emerging-role-for-microglia
#19
REVIEW
Sami Piirainen, Andrew Youssef, Cai Song, Allan V Kalueff, Gary E Landreth, Tarja Malm, Li Tian
Chronic psychosocial stress is increasingly recognized as a risk factor for late-onset Alzheimer's disease (LOAD) and associated cognitive deficits. Chronic stress also primes microglia and induces inflammatory responses in the adult brain, thereby compromising synapse-supportive roles of microglia and deteriorating cognitive functions during aging. Substantial evidence demonstrates that failure of microglia to clear abnormally accumulating amyloid-beta (Aβ) peptide contributes to neuroinflammation and neurodegeneration in AD...
February 6, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28183994/optimal-reference-region-to-measure-longitudinal-amyloid-beta-change-with-18-f-florbetaben-pet
#20
Santiago Bullich, Victor L Villemagne, Ana M Catafau, Aleksandar Jovalekic, Norman Koglin, Christopher C Rowe, Susan De Santi
Accurate measurement of changes in amyloid-beta (Aβ) deposition over time is important in longitudinal studies, particularly in anti-Aβ therapeutic trials. To achieve this, the optimal reference region (RR) must be selected to reduce variance of Aβ positron emission tomography (PET) measurements, allowing early detection of treatment efficacy. The aim of this study was to determine the RR that allows earlier detection of subtle Aβ changes using (18)F florbetaben (FBB) PET. Methods: Forty-five patients with mild cognitive impairment (MCI) (72...
February 9, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
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