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https://www.readbyqxmd.com/read/28813012/inhibitory-effect-of-lycopene-on-amyloid-%C3%AE-induced-apoptosis-in-neuronal-cells
#1
Sinwoo Hwang, Joo Weon Lim, Hyeyoung Kim
Alzheimer's disease (AD) is a fatal neurodegenerative disease. Brain amyloid-β deposition is a crucial feature of AD, causing neuronal cell death by inducing oxidative damage. Reactive oxygen species (ROS) activate NF-κB, which induces expression of Nucling. Nucling is a pro-apoptotic factor recruiting the apoptosome complex. Lycopene is an antioxidant protecting from oxidative stress-induced cell damage. We investigated whether lycopene inhibits amyloid-β-stimulated apoptosis through reducing ROS and inhibiting mitochondrial dysfunction and NF-κB-mediated Nucling expression in neuronal SH-SY5Y cells...
August 16, 2017: Nutrients
https://www.readbyqxmd.com/read/28811267/app-a%C3%AE-structural-diversity-and-alzheimer-s-disease-pathogenesis
#2
REVIEW
Alex E Roher, Tyler A Kokjohn, Steven G Clarke, Michael R Sierks, Chera L Maarouf, Geidy E Serrano, Marwan S Sabbagh, Thomas G Beach
The amyloid cascade hypothesis of Alzheimer's disease (AD) proposes amyloid- β (Aβ) is a chief pathological element of dementia. AD therapies have targeted monomeric and oligomeric Aβ 1-40 and 1-42 peptides. However, alternative APP proteolytic processing produces a complex roster of Aβ species. In addition, Aβ peptides are subject to extensive posttranslational modification (PTM). We propose that amplified production of some APP/Aβ species, perhaps exacerbated by differential gene expression and reduced peptide degradation, creates a diverse spectrum of modified species which disrupt brain homeostasis and accelerate AD neurodegeneration...
August 12, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28811138/intermittent-hypoxia-training-powerful-non-invasive-cerebroprotection-against-ethanol-withdrawal-excitotoxicity
#3
REVIEW
Marianna E Jung, Robert T Mallet
Ethanol intoxication and withdrawal exact a devastating toll on the central nervous system. Abrupt ethanol withdrawal provokes massive release of the excitatory neurotransmitter glutamate, which over-activates its postsynaptic receptors, causing intense Ca(2+) loading, p38 mitogen activated protein kinase activation and oxidative stress, culminating in ATP depletion, mitochondrial injury, amyloid β deposition and neuronal death. Collectively, these mechanisms produce neurocognitive and sensorimotor dysfunction that discourages continued abstinence...
August 12, 2017: Respiratory Physiology & Neurobiology
https://www.readbyqxmd.com/read/28808293/targeting-apolipoprotein-e-amyloid-%C3%AE-binding-by-peptoid-cpo_a%C3%AE-17-21%C3%A2-p-ameliorates-alzheimer-s-disease-related-pathology-and-cognitive-decline
#4
Shan Liu, Shinae Park, Grant Allington, Frances Prelli, Yanjie Sun, Mitchell Martá-Ariza, Henrieta Scholtzova, Goutam Biswas, Bernard Brown, Philip B Verghese, Pankaj D Mehta, Yong-Uk Kwon, Thomas Wisniewski
Inheritance of the apolipoprotein E4 (apoE4) genotype has been identified as the major genetic risk factor for late onset Alzheimer's disease (AD). Studies have shown that apoE, apoE4 in particular, binds to amyloid-β (Aβ) peptides at residues 12-28 of Aβ and this binding modulates Aβ accumulation and disease progression. We have previously shown in several AD transgenic mice lines that blocking the apoE/Aβ interaction with Aβ12-28 P reduced Aβ and tau-related pathology, leading to cognitive improvements in treated AD mice...
August 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28808140/amyloid-%C3%AE-and-islet-amyloid-pathologies-link-alzheimer-disease-and-type-2-diabetes-in-a-transgenic-model
#5
Nadeeja Wijesekara, Rosemary Ahrens, Miheer Sabale, Ling Wu, Kathy Ha, Giuseppe Verdile, Paul E Fraser
Alzheimer's disease (AD) and type 2 diabetes (T2D) present a significant risk to each other. AD and T2D are characterized by deposition of cerebral amyloid-β (Aβ) and pancreatic human islet amyloid polypeptide (hIAPP), respectively. We investigated the role of amyloidogenic proteins in the interplay between these diseases. A novel double transgenic mouse model combining T2D and AD was generated and characterized. AD-related amyloid transgenic mice coexpressing hIAPP displayed peripheral insulin resistance, hyperglycemia, and glucose intolerance...
August 14, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28806762/a-becn1-mutation-mediates-hyperactive-autophagic-sequestration-of-amyloid-oligomers-and-improved-cognition-in-alzheimer-s-disease
#6
Altea Rocchi, Soh Yamamoto, Tabitha Ting, Yuying Fan, Katherine Sadleir, Yigang Wang, Weiran Zhang, Sui Huang, Beth Levine, Robert Vassar, Congcong He
Impairment of the autophagy pathway has been observed during the pathogenesis of Alzheimer's disease (AD), a neurodegenerative disorder characterized by abnormal deposition of extracellular and intracellular amyloid β (Aβ) peptides. Yet the role of autophagy in Aβ production and AD progression is complex. To study whether increased basal autophagy plays a beneficial role in Aβ clearance and cognitive improvement, we developed a novel genetic model to hyperactivate autophagy in vivo. We found that knock-in of a point mutation F121A in the essential autophagy gene Beclin 1/Becn1 in mice significantly reduces the interaction of BECN1 with its inhibitor BCL2, and thus leads to constitutively active autophagy even under non-autophagy-inducing conditions in multiple tissues, including brain...
August 14, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28805003/protein-astrogliopathies-in-human-neurodegenerative-diseases-and-aging
#7
Gabor G Kovacs, Virginia M Lee, John Q Trojanowski
Neurodegenerative diseases are characterized by progressive dysfunction and loss of neurons associated with depositions of pathologically altered proteins showing hierarchical involvement of brain regions. The role of astrocytes in the pathogenesis of neurodegenerative diseases is explored as contributors to neuronal degeneration or neuroprotection pathways, and also as potential mediators of the transcellular spreading of disease-associated proteins. Protein astrogliopathy (PAG), including deposition of amyloid-β, prion protein, tau, α-synuclein, and very rarely transactive response DNA-binding protein 43 (TDP-43) is not unprecedented or unusual in neurodegenerative diseases...
September 2017: Brain Pathology
https://www.readbyqxmd.com/read/28803064/high-glucose-induces-tau-hyperphosphorylation-through-activation-of-tlr9-p38mapk-pathway
#8
Yue Sun, Qian Xiao, Cheng Luo, Yuxing Zhao, Die Pu, Kexiang Zhao, Jinliang Chen, Meili Wang, Zhiyin Liao
Diabetic encephalopathy (DE) is one of the most common complications of diabetes. The major pathological variations include neurofibrillary tangles (NFTs), which are caused by tau hyperphosphorylation, and senile plaques (SPs) consisting of amyloid β- protein(Aβ) deposits. In recent years, DE research studies have focused on exploring the activation of the inflammatory signaling pathway in immune cells. Toll-like receptor 9 (TLR9) is well known to regulate the inflammatory reactions in immune processes. During the tau hyperphosphorylation process, TLR9 in microglia plays bidirectional roles...
August 9, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28802916/brain-region-and-sex-specific-alterations-in-mitochondrial-function-and-nf-%C3%AE%C2%BAb-signaling-in-the-tgcrnd8-mouse-model-of-alzheimer-s-disease
#9
Jelena Djordjevic, Ella Thomson, Subir Roy Chowdhury, Wanda M Snow, Claudia Perez, Tak Pan Wong, Paul Fernyhough, Benedict C Albensi
Alzheimer's disease (AD) is the most common late onset neurodegenerative disorder with indications that women are disproportionally affected. Mitochondrial dysfunction has been one of the most discussed hypotheses associated with the early onset and progression of AD, and it has been attributed to intraneuronal accumulation of amyloid β (Aβ). It was suggested that one of the possible mediators for Aβ-impaired mitochondrial function is the nuclear factor kappa B (NF-κB) signaling pathway. NF-κB plays important roles in brain inflammation and antioxidant defense, as well as in the regulation of mitochondrial function, and studies have confirmed altered NF-κB signaling in AD brain...
August 9, 2017: Neuroscience
https://www.readbyqxmd.com/read/28802038/trem2-maintains-microglial-metabolic-fitness-in-alzheimer-s-disease
#10
Tyler K Ulland, Wilbur M Song, Stanley Ching-Cheng Huang, Jason D Ulrich, Alexey Sergushichev, Wandy L Beatty, Alexander A Loboda, Yingyue Zhou, Nigel J Cairns, Amal Kambal, Ekaterina Loginicheva, Susan Gilfillan, Marina Cella, Herbert W Virgin, Emil R Unanue, Yaming Wang, Maxim N Artyomov, David M Holtzman, Marco Colonna
Elevated risk of developing Alzheimer's disease (AD) is associated with hypomorphic variants of TREM2, a surface receptor required for microglial responses to neurodegeneration, including proliferation, survival, clustering, and phagocytosis. How TREM2 promotes such diverse responses is unknown. Here, we find that microglia in AD patients carrying TREM2 risk variants and TREM2-deficient mice with AD-like pathology have abundant autophagic vesicles, as do TREM2-deficient macrophages under growth-factor limitation or endoplasmic reticulum (ER) stress...
August 10, 2017: Cell
https://www.readbyqxmd.com/read/28800330/pet-tau-and-amyloid-%C3%AE-burden-in-mild-alzheimer-s-disease-divergent-relationship-with-age-cognition-and-cerebrospinal-fluid-biomarkers
#11
Ivan Koychev, Roger N Gunn, Azadeh Firouzian, Jennifer Lawson, Giovanna Zamboni, Basil Ridha, Barbara J Sahakian, James B Rowe, Alan Thomas, Lynn Rochester, Dominic Ffytche, Robert Howard, Henrik Zetterberg, Clare MacKay, Simon Lovestone
BACKGROUND: Combining PET amyloid-β (Aβ) and tau imaging may be critical for tracking disease progression in Alzheimer's disease (AD). OBJECTIVE: We sought to characterize the relationship between Aβ and tau ligands as well as with other measures of pathology. METHODS: We conducted a multi-center observational study in early AD (MMSE >20) participants aged 50 to 85 y. The schedule included cognitive assessments (ADAS-Cog) and CSF measurement of Aβ and tau at baseline and 6 months; PET-CT imaging with Aβ ([18F]AV45) and tau ([18F]AV1451) ligands at baseline...
August 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28800326/intracerebroventricular-streptozotocin-induces-obesity-and-dementia-in-lewis-rats-rat-model-of-dementia-associated-with-obesity
#12
Konstantin Bloch, Irit Gil-Ad, Alexey Vanichkin, Shay Henry Hornfeld, Nickolay Koroukhov, Michal Taler, Pnina Vardi, Abraham Weizman
BACKGROUND: Animal models of dementia associated with metabolic abnormalities play an important role in understanding the bidirectional relationships between these pathologies. Rodent strains develop cognitive dysfunctions without alteration of peripheral metabolism following intracerebroventricular administration of streptozotocin (icv-STZ). OBJECTIVE: We aimed to estimate the effect of icv-STZ on cognitive functions and peripheral metabolism in Lewis rats, which are rarely used for the induction of cognitive abnormalities...
August 8, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28799137/ethanol-alters-app-processing-and-aggravates-alzheimer-associated-phenotypes
#13
Daochao Huang, Mengjiao Yu, Shou Yang, Dandan Lou, Weitao Zhou, Lingling Zheng, Zhe Wang, Fang Cai, Weihui Zhou, Tingyu Li, Weihong Song
The majority of Alzheimer's disease (AD) cases are sporadic with unknown causes. Many dietary factors including excessive alcohol intake have been reported to increase the risk to develop AD. The effect of alcohol on cognitive functions and AD pathogenesis remains elusive. In this study, we investigated the relationship between ethanol exposure and Alzheimer's disease. Cell cultures were treated with ethanol at different dosages for different durations up to 48 h and an AD model mouse was fed with ethanol for 4 weeks...
August 10, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28798664/interplay-of-energetics-and-er-stress-exacerbates-alzheimer-s-amyloid-%C3%AE-a%C3%AE-toxicity-in-yeast
#14
Xin Chen, Markus M M Bisschops, Nisha R Agarwal, Boyang Ji, Kumaravel P Shanmugavel, Dina Petranovic
Alzheimer's disease (AD) is a progressive neurodegeneration. Oligomers of amyloid-β peptides (Aβ) are thought to play a pivotal role in AD pathogenesis, yet the mechanisms involved remain unclear. Two major isoforms of Aβ associated with AD are Aβ40 and Aβ42, the latter being more toxic and prone to form oligomers. Here, we took a systems biology approach to study two humanized yeast AD models which expressed either Aβ40 or Aβ42 in bioreactor cultures. Strict control of oxygen availability and culture pH, strongly affected chronological lifespan and reduced variations during cell growth...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28798397/sleep-mediates-the-association-between-homocysteine-and-oxidative-status-in-mild-cognitive-impairment
#15
Mayely P Sanchez-Espinosa, Mercedes Atienza, Jose L Cantero
Tremendous progress has been made over the last few years in understanding how sleep and amyloid-β (Aβ) cooperate to speed up the progression of Alzheimer's disease (AD). However, it remains unknown whether sleep deficits also interact with other risk factors that exacerbate the pathological cascade of AD. Based on evidence showing that higher levels of homocysteine (HCY) and sleep loss increase oxidative damage, we here investigate whether the relationship between HCY and total antioxidant capacity (TAC) is mediated by changes in objective sleep in healthy older (HO, N = 21) and mild cognitive impairment (MCI, N = 21) subjects...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28796507/molecular-dynamics-study-to-investigate-the-dimeric-structure-of-the-full-length-%C3%AE-synuclein-in-aqueous-solution
#16
Tingting Zhang, Yuanxin Tian, Zhonghuang Li, Siming Liu, Xiang Hu, Zichao Yang, Xiaotong Ling, Shu-Wen Liu, Jiajie Zhang
The mechanisms of dimerization of α-Synuclein from full-length monomers and the structural features have been investigated through molecular dynamics simulations in this study. The dimerization of α-Syn plays a critical role in the fibrillogenesis mechanism and could initiate and trigger α-Syn to aggregate by conformational transforming. According to the alignment between three regions of α-Syn monomer, 8 diverse starting structures have been constructed. However, only 5 configurations show the dimeric structures and the detailed properties of 3 dimers of them are discussed...
August 10, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/28796251/differential-spatial-expression-of-peripheral-olfactory-neuron-derived-bace1-induces-olfactory-impairment-by-region-specific-accumulation-of-%C3%AE-amyloid-oligomer
#17
Seung-Jun Yoo, Ji-Hye Lee, So Yeun Kim, Gowoon Son, Jae Yeon Kim, Bongki Cho, Seong-Woon Yu, Keun-A Chang, Yoo-Hun Suh, Cheil Moon
Olfactory dysfunction is a common symptom associated with neurodegenerative diseases including Alzheimer's disease (AD). Although evidence exists to suggest that peripheral olfactory organs are involved in the olfactory dysfunction that accompanies AD pathology, the underlying mechanisms are not fully understood. As confirmed using behavioral tests, transgenic mice overexpressing a Swedish mutant form of human amyloid precursor proteins exhibited olfactory impairments prior to evidence of cognitive impairment...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28791538/attenuation-of-neurobehavioral-and-neurochemical-abnormalities-in-animal-model-of-cognitive-deficits-of-alzheimer-s-disease-by-fermented-soybean-nanonutraceutical
#18
Vikas Kumar, Prakash Chandra Bhatt, Shruti Pathak, Bibhu Prasad Panda
The present study was performed to evaluate the efficacy of nanonutraceuticals (NN) for attenuation of neurobehavioral and neurochemical abnormalities in Alzheimer's disease. Solid-state fermentation of soybean with Bacillus subtilis was performed to produce different metabolites (nattokinase, daidzin, genistin and glycitin and menaquinone-7). Intoxication of rats with colchicine caused impairment in learning and memory which was demonstrated in neurobehavioral paradigms (Morris water maze and passive avoidance) linked with decreased activity of acetylcholinesterase (AChE)...
August 8, 2017: Inflammopharmacology
https://www.readbyqxmd.com/read/28791490/secretases-related-mirnas-in-alzheimer-s-disease-new-approach-for-biomarker-discovery
#19
REVIEW
Seyedeh Nazanin Hajjari, Mehdi Mehdizadeh, Saeed Sadigh-Eteghad, Dariush Shanehbandi, Shahram Teimourian, Behzad Baradaran
Amyloid-β (Aβ) as a crucial factor in pathogenesis of Alzheimer's disease (AD) is derived from amyloid precursor protein (APP) through a proteolytic process catalyzing by β- and γ-secretase-in amyloidogenesis pathway. Products of α-secretase cleavage also have protective effects against Aβ toxicity. According to existing evidences, microRNAs (miRNAs) show a unique pattern of expression in AD. Moreover, miRNAs regulatory effects on expression of secretases and their main components have been demonstrated in AD...
August 8, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28790798/development-and-characterisation-of-a-novel-nf-%C3%AE%C2%BAb-reporter-cell-line-for-investigation-of-neuroinflammation
#20
Marie-Theres Zeuner, Thomas Vallance, Sakthivel Vaiyapuri, Graeme S Cottrell, Darius Widera
Aberrant activation of the transcription factor NF-κB, as well as uncontrolled inflammation, has been linked to autoimmune diseases, development and progression of cancer, and neurological disorders like Alzheimer's disease. Reporter cell lines are a valuable state-of-the art tool for comparative analysis of in vitro drug screening. However, a reporter cell line for the investigation of NF-κB-driven neuroinflammation has not been available. Thus, we developed a stable neural NF-κB-reporter cell line to assess the potency of proinflammatory molecules and peptides, as well as anti-inflammatory pharmaceuticals...
2017: Mediators of Inflammation
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