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https://www.readbyqxmd.com/read/29782912/in-vitro-protective-activity-of-south-australian-marine-sponge-and-macroalgae-extracts-against-amyloid-beta-a%C3%AE-1-42-induced-neurotoxicity-in-pc-12-cells
#1
Mousa Alghazwi, Scott Smid, Wei Zhang
South Australia is a biodiversity hotspot of marine sponges and macroalgae. This study aimed to evaluate the potential neuroprotective activity of extracts from these two marine sources by reducing the toxicity of human amyloid beta Aβ1-42 in a cell model assay using PC-12 cells. A total of 92 extracts (43, 13, 16, and 20 extracts from sponge of 8 orders and 17 families, green algae of 3 orders and 4 families, brown algae of 6 orders and 8 families, and red algae of 5 orders and 10 families, respectively) were initially screened at three different concentrations (0...
May 18, 2018: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/29782911/estrogen-deficiency-exacerbates-a%C3%AE-induced-memory-impairment-through-enhancement-of-neuroinflammation-amylodogenesis-and-nf-%C3%A4-b-activation-in-ovariectomized-mice
#2
Jaesuk Yun, In Jun Yeo, Chul Ju Hwang, Dong-Young Choi, Hyung-Sik Im, Ji Youg Kim, Won Rak Choi, Myung Hee Jung, Sang-Bae Han, Jin Tae Hong
Estrogen is well known to have a preventative effect in Alzheimer's disease (AD) pathology. Several studies have demonstrated that nuclear factor kappa-B (NF-ĸB) can contribute to the effects of estrogen on the development of AD. We investigated whether NF-ĸB affects amyloid-beta (Aβ)-induced memory impairment in an estrogen-lacking condition. In the present study, nine-week-old Institute cancer research (ICR) mice were ovariectomized to block estrogen stimulation. Ten weeks after the ovariectomization, mice were administered with Aβ (300 pmol) via intracerebroventricular (ICV) infusion for 2 weeks...
May 18, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29781021/dynamical-crossover-of-water-confined-within-the-amphiphilic-nanocores-of-aggregated-amyloid-%C3%AE-peptides
#3
Prabir Khatua, Sanjoy Bandyopadhyay
It is believed that the self-assembly of amyloid beta (Aβ) peptides in the brain is the cause of Alzheimer's disease. Atomistic molecular dynamics simulations of aqueous solutions of Aβ protofilaments of different sizes at room temperature have been carried out to explore the dynamic properties of water confined within the core and at the exterior surface of the protofilaments. Attempts have been made to understand how the non-uniform distortion of the protofilaments associated with their structural crossover influences the diffusivity and the hydrogen bonding environment of the confined water molecules...
May 21, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29780824/clinical-histological-and-immunohistochemical-findings-in-inclusion-body-myositis
#4
Leonardo Valente de Camargo, Mary Souza de Carvalho, Samuel Katsuyuki Shinjo, Acary Souza Bulle de Oliveira, Edmar Zanoteli
Sporadic inclusion body myositis (sIBM) is considered the most common acquired myopathy aged over 50 years. The disease is characterized by a particular process of muscle degeneration characterized by abnormal deposit of protein aggregates in association with inflammation. The aim of this study was to present clinical and muscle histopathological findings, including immunostaining for LC3B, p62, α -synuclein, and TDP-43, in 18 patients with sIBM. The disease predominated in males (61%) and European descendants, with onset of clinical manifestations around 59 years old...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29777707/functional-analysis-of-juxta-and-intra-membrane-domains-of-murine-app-by-genome-editing-in-neuro2a-cells
#5
Nanaka Kaneshiro, Ryosuke Imaoka, Masato Komai, Taku Kashiyama, Takashi Sakurai, Takashi Uehara, Nobumasa Takasugi
Amyloid-β precursor protein (APP) correlates with the pathogenesis of certain brain diseases, such as Alzheimer disease (AD). APP is cleaved by several enzymes to produce APP metabolites, including the amyloid beta peptide (Aβ), which accumulates in the brain of AD patients. However, the exact functions of APP metabolites remain elusive. In this study, using genome editing technology, we mutated juxta- and intra-membrane domains of murine APP in the mouse neuroblastoma cell line, Neuro2a. We identified several clones that expressed characteristic patterns of APP metabolites...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777699/cart-peptide-activates-the-nrf2-ho-1-antioxidant-pathway-and-protects-hippocampal-neurons-in-a-rat-model-of-alzheimer-s-disease
#6
Wenyu Jiao, Yongchen Wang, Linghong Kong, Tao Ou-Yang, Qing Meng, Qiang Fu, Zhenzhen Hu
The accumulation of amyloid-beta (Aβ) and oxidative stress damage in the brain are recognized as early features of Alzheimer's disease (AD). The cocaine- and amphetamine-regulated transcript (CART) peptide may possibly play an antioxidative role in neurons. The aim of this study was to investigate the potential antioxidant mechanism of CART peptide in a rat model of AD. We microinjected of Aβ1-42 (2μl/4μg/hemisphere) into rat hippocampus to set a rat model of AD. A pre-microinjection of CART peptide (1μl/0...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777051/cd36-initiates-the-secretory-phenotype-during-the-establishment-of-cellular-senescence
#7
Mengyang Chong, Tao Yin, Rui Chen, Handan Xiang, Lifeng Yuan, Yi Ding, Christopher C Pan, Zhen Tang, Peter B Alexander, Yinjun Jia, Qi-Jing Li, Xiao-Fan Wang
Cellular senescence is a unique cell fate characterized by stable proliferative arrest and the extensive production and secretion of various inflammatory proteins, a phenomenon known as the senescence-associated secretory phenotype (SASP). The molecular mechanisms responsible for generating a SASP in response to senescent stimuli remain largely obscure. Here, using unbiased gene expression profiling, we discover that the scavenger receptor CD36 is rapidly upregulated in multiple cell types in response to replicative, oncogenic, and chemical senescent stimuli...
May 18, 2018: EMBO Reports
https://www.readbyqxmd.com/read/29777003/impact-of-reference-target-region-selection-on-amyloid-pet-standard-uptake-value-ratios-in-the-phase-1b-prime-study-of-aducanumab
#8
Ping Chiao, Barry J Bedell, Brian Avants, Alex P Zijdenbos, Marilyn Grand'Maison, Paul O'Neill, John O'Gorman, Tianle Chen, Robert Koeppe
Standardized uptake value ratios (SUVRs) are commonly used to quantify tracer uptake in amyloid beta positron emission tomography (Aβ-PET). Here, we explore the impact of target and reference region of interest (ROI) selection on SUVR effect size using interventional data from the ongoing Phase Ib PRIME study (NCT01677572) of aducanumab (BIIB037) in patients with prodromal or mild Alzheimer's disease (AD). Methods: Florbetapir PET SUVR was calculated at baseline (screening) and Weeks 26 and 54 for patients randomized to placebo and each of four aducanumab doses (1, 3, 6, and 10 mg/kg), using whole cerebellum, cerebellar grey matter, cerebellar white matter, pons, and subcortical white matter as reference regions...
May 18, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29775750/the-effects-of-capn1-gene-inactivation-on-the-differential-expression-of-genes-in-skeletal-muscle
#9
William T Olive, Brittney N Keel, Amanda K Lindholm-Perry, Justyna Horodyska, Andrew P Foote
Protein turnover is required for muscle growth and regeneration and several proteolytic enzymes, including the calpains, degrade myofibrillar proteins during this process. In a previous experiment, phenotypic differences were observed between μ-calpain knockout (KO) and wild type (WT) mice, including nutrient accretion and fiber type differences. These changes were particularly evident as the animals aged. Thus, we utilized 18 mice (9 KO and 9 WT) to compare transcript abundance to identify differentially expressed genes (DEGs) at 52 wk of age...
May 15, 2018: Gene
https://www.readbyqxmd.com/read/29775277/cid-9998128-compound-is-a-potential-multi-target-drug-for-alzheimer-s-disease
#10
Nguyen Quoc Thai, Zuzana Bednarikova, Miroslav Gancar, Huynh Quang Linh, Chin-Kun Hu, Mai Suan Li, Zuzana Gazova
We have probed capability of small CID 9998128 compound as a potential multi-target drug for the Alzheimer's disease (AD) using in silico and in vitro experiments. By all-atom simulation and MM-PBSA method we have demonstrated that this compound strongly binds to both amyloid beta 42 (Aβ42 ) fibrils and β-secretase and the van der Waals interaction is dominating over the electrostatic interaction in binding affinity. A detailed analysis at the atomic level revealed that indazole in CID 99998128 structure made a major contribution to instability of all studied complexes...
May 18, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29772299/biophenols-enzymes-%C3%AE-secretase-cholinesterases-histone-deacetylase-and-tyrosinase-inhibitors-from-olive-olea-europaea-l
#11
Syed Haris Omar, Christopher J Scott, Adam S Hamlin, Hassan K Obied
The focus of this study was on inhibition of enzymes involved in the pathogenesis Alzheimer's disease (AD) including prime amyloid beta (Aβ) producing enzyme (β-secretase: BACE-1) and disease progression enzymes including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), histone deacetylase (HDAC), and tyrosinase along with the catecholamine L-DOPA, by using olive biophenols. Here we report the strongest inhibition of BACE-1 from rutin (IC50 : 3.8 nM) followed by verbascoside (IC50 : 6.3 nM) and olive fruit extract (IC50 : 18 ng), respectively...
May 14, 2018: Fitoterapia
https://www.readbyqxmd.com/read/29764912/mitochondrial-pitrm1-peptidase-loss-of-function-in-childhood-cerebellar-atrophy
#12
Yeshaya Langer, Adi Aran, Suleyman Gulsuner, Bassam Abu Libdeh, Paul Renbaum, Dario Brunetti, Pedro-Filipe Teixeira, Tom Walsh, Sharon Zeligson, Roberta Ruotolo, Rachel Beeri, Imad Dweikat, Maher Shahrour, Ariella Weinberg-Shukron, Fouad Zahdeh, Enrico Baruffini, Elzbieta Glaser, Mary-Claire King, Ephrat Levy-Lahad, Massimo Zeviani, Reeval Segel
OBJECTIVE: To identify the genetic basis of a childhood-onset syndrome of variable severity characterised by progressive spinocerebellar ataxia, mental retardation, psychotic episodes and cerebellar atrophy. METHODS: Identification of the underlying mutations by whole exome and whole genome sequencing. Consequences were examined in patients' cells and in yeast. RESULTS: Two brothers from a consanguineous Palestinian family presented with progressive spinocerebellar ataxia, mental retardation and psychotic episodes...
May 15, 2018: Journal of Medical Genetics
https://www.readbyqxmd.com/read/29763806/a-review-on-flavonoid-based-scaffolds-as-multi-target-directed-ligands-mtdls-for-alzheimer-s-disease
#13
REVIEW
Leili Jalili-Baleh, Elaheh Babaei, Shahin Abdpour, Syed Nasir Abbas Bukhari, Alireza Foroumadi, Ali Ramazani, Mohammad Sharifzadeh, Mohammad Abdollahi, Mehdi Khoobi
Alzheimer's disease (AD), the most common form of dementia, is a multifactorial neurodegenerative disease. The target enzymes inhibition including cholinesterase, beta-secretase, monoamine oxidase and inhibition of amyloid-β aggregation as well as oxidative stress and metal chelation play an important role in the pathogenesis of AD. Chroman-4-one scaffold with benzo-γ-pyrone network is a privileged structure in organic synthesis and drug design. A large number of research has been carried out on modified naturally occurring chromanone scaffolds and/or synthesized new analogues, to obtain effective drugs for AD management...
May 7, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29762152/alzheimer-s-disease-neuroimaging
#14
Jennifer L Whitwell
PURPOSE OF REVIEW: The aim of this study was to discuss the contribution of neuroimaging studies to our understanding of Alzheimer's disease. We now have the capability of measuring both tau and beta-amyloid (Aβ) proteins in the brain, which together with more traditional neuroimaging modalities, has led the field to focus on using neuroimaging to better characterize disease mechanisms underlying Alzheimer's disease. RECENT FINDINGS: Studies have utilized tau and Aβ PET, as well as [18F]fluorodeoxyglucose PET, and structural and functional MRI, to investigate the following topics: phenotypic variability in Alzheimer's disease , including how neuroimaging findings are related to clinical phenotype and age; multimodality analyses to investigate the relationships between different neuroimaging modalities and what that teaches us about disease mechanisms; disease staging by assessing neuroimaging changes in the very earliest phases of the disease in cognitively normal individuals and individuals carrying an autosomal dominant Alzheimer's disease mutation; and influence of other comorbidities and proteins to the disease process...
May 11, 2018: Current Opinion in Neurology
https://www.readbyqxmd.com/read/29759078/transcriptome-analysis-of-alcohol-treated-microglia-reveals-downregulation-of-beta-amyloid-phagocytosis
#15
Sergey Kalinin, Marta González-Prieto, Hannah Scheiblich, Lucia Lisi, Handojo Kusumo, Michael T Heneka, Jose L M Madrigal, Subhash C Pandey, Douglas L Feinstein
BACKGROUND: Microglial activation contributes to the neuropathology associated with chronic alcohol exposure and withdrawal, including the expression of inflammatory and anti-inflammatory genes. In the current study, we examined the transcriptome of primary rat microglial cells following incubation with alcohol alone, or alcohol together with a robust inflammatory stimulus. METHODS: Primary microglia were prepared from mixed rat glial cultures. Cells were incubated with 75 mM ethanol alone or with proinflammatory cytokines ("TII": IL1β, IFNγ, and TNFα)...
May 14, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29757200/a-rationally-designed-hsp70-variant-rescues-the-aggregation-associated-toxicity-of-human-iapp-in-cultured-pancreatic-islet-%C3%AE-cells
#16
Marie Nicole Bongiovanni, Francesco Antonio Aprile, Pietro Sormanni, Michele Vendruscolo
Molecular chaperones are key components of the protein homeostasis system against protein misfolding and aggregation. It has been recently shown that these molecules can be rationally modified to have an enhanced activity against specific amyloidogenic substrates. The resulting molecular chaperone variants can be effective inhibitors of protein aggregation in vitro, thus suggesting that they may provide novel opportunities in biomedical and biotechnological applications. Before such opportunities can be exploited, however, their effects on cell viability should be better characterised...
May 12, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29755842/lipopolysaccharide-endotoxemia-induces-amyloid-%C3%AE-and-p-tau-formation-in-the-rat-brain
#17
Li-Ming Wang, Qi Wu, Ryan A Kirk, Kevin P Horn, Ahmed H Ebada Salem, John M Hoffman, Jeffrey T Yap, Joshua A Sonnen, Rheal A Towner, Fernando A Bozza, Rosana S Rodrigues, Kathryn A Morton
Amyloid beta (Aβ) plaques are not specific to Alzheimer's disease and occur with aging and neurodegenerative disorders. Soluble brain Aβ may be neuroprotective and increases in response to neuroinflammation. Sepsis is associated with neurocognitive compromise. The objective was to determine, in a rat endotoxemia model of sepsis, whether neuroinflammation and soluble Aβ production are associated with Aβ plaque and hyperphosphorylated tau deposition in the brain. Male Sprague Dawley rats received a single intraperitoneal injection of 10 mg/kg of lipopolysaccharide endotoxin (LPS)...
2018: American Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29755512/proton-pump-inhibitors-and-dementia-physiopathological-mechanisms-and-clinical-consequences
#18
REVIEW
Gloria Ortiz-Guerrero, Diana Amador-Muñoz, Carlos Alberto Calderón-Ospina, Daniel López-Fuentes, Mauricio Orlando Nava Mesa
Alzheimer's disease (AD) is the most common type of dementia, mainly encompassing cognitive decline in subjects aged ≥65 years. Further, AD is characterized by selective synaptic and neuronal degeneration, vascular dysfunction, and two histopathological features: extracellular amyloid plaques composed of amyloid beta peptide (A β ) and neurofibrillary tangles formed by hyperphosphorylated tau protein. Dementia and AD are chronic neurodegenerative conditions with a complex physiopathology involving both genetic and environmental factors...
2018: Neural Plasticity
https://www.readbyqxmd.com/read/29755351/gastrodin-attenuates-bilateral-common-carotid-artery-occlusion-induced-cognitive-deficits-via-regulating-a%C3%AE-related-proteins-and-reducing-autophagy-and-apoptosis-in-rats
#19
Bo Liu, Jian-Mei Gao, Fei Li, Qi-Hai Gong, Jing-Shan Shi
Gastrodin (GAS), an active constituent extracted from Gastrodia elata Blume, is used to treat ischemic stroke, epilepsy, dizziness, and dementia for centuries in China. This study examined its effects on vascular dementia (VD) and the underlying molecular mechanisms. VD was established by ligation of bilateral common carotid artery occlusion (BCCAO). A total of 7 days after BCCAO surgery, GAS (15, 30, and 60 mg/kg) was orally administered for 28 consecutive days to evaluate therapeutic effects. Cognitive function was tested by the Morris water maze...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29755341/plasma-biomarkers-differentiate-parkinson-s-disease-from-atypical-parkinsonism-syndromes
#20
Chin-Hsien Lin, Shieh-Yueh Yang, Herng-Er Horng, Che-Chuan Yang, Jen-Jie Chieh, Hsin-Hsien Chen, Bing-Hsien Liu, Ming-Jang Chiu
Objective: Parkinson's disease (PD) has significant clinical overlaps with atypical parkinsonism syndromes (APS), which have a poorer treatment response and a more aggressive course than PD. We aimed to identify plasma biomarkers to differentiate PD from APS. Methods: Plasma samples ( n = 204) were obtained from healthy controls and from patients with PD, dementia with Lewy bodies (DLB), multiple system atrophy, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), or frontotemporal dementia (FTD) with parkinsonism (FTD-P) or without parkinsonism...
2018: Frontiers in Aging Neuroscience
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