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Xin Yu, Pei-Pei Guan, Di Zhu, Yun-Yue Liang, Tao Wang, Zhan-You Wang, Pu Wang
Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment. The neuropathological features of AD are the aggregation of extracellular amyloid β-protein (Aβ) and tau phosphorylation. Recently, AD was found to be associated with magnesium ion (Mg2+ ) deficit and tumor necrosis factor-alpha (TNF-α) elevation in the serum or brains of AD patients. To study the relationship between Mg2+ and TNF-α, we used human- or mouse-derived glial and neuronal cell lines or APP/PS1 transgenic (Tg) mice as in vitro and in vivo experimental models, respectively...
2018: Frontiers in Molecular Neuroscience
Qing-Hua Yang, Ling Guo, Qing Chen, Kai-Hui Wu, Yan-Jun Wu, Yan Jia, Shu-Juan Zhu, Cheng-Lin Tang, Hua-Jun Sheng
OBJECTIVE: To observe the effect of electroacupuncture (EA) intervention on learning-memory ability and the expression of senile plaques (SP), amyloid precursor protein (APP), β-secretase 1(BACE 1) and insulin degrading enzyme (IDE) in the hippocampus in APP/presenilin 1 (PS 1) double transgenic Alzheimer's disease (AD) mice, so as to reveal its mechanisms underlying improvement of AD. METHODS: A total of 18 male APP/PS 1 double transgenic AD mice were randomly divided into model, EA-2-week and EA-3-week groups ( n =6 in each)...
April 25, 2018: Zhen Ci Yan Jiu, Acupuncture Research
Katarzyna Marta Zoltowska, Masato Maesako, Joshua Meier, Oksana Berezovska
Neuronal hyperactivity is one of the earliest events observed in Alzheimer's disease (AD). Moreover, alterations in the expression of glutamate transporters have been reported to exacerbate amyloid pathology and cognitive deficits in transgenic AD mouse models. However, the molecular links between these pathophysiological changes remain largely unknown. Here, we report novel interaction between presenilin 1 (PS1), the catalytic component of the amyloid precursor protein-processing enzyme, γ-secretase, and a major glutamate transporter-1 (GLT-1)...
June 7, 2018: Scientific Reports
Yanmei Zhao, Chieh-Hsiang Tan, Amber Krauchunas, Andrea Scharf, Nicholas Dietrich, Kurt Warnhoff, Zhiheng Yuan, Marina Druzhinina, Sam Guoping Gu, Long Miao, Andrew Singson, Ronald E Ellis, Kerry Kornfeld
Sperm activation is a fascinating example of cell differentiation, in which immotile spermatids undergo a rapid and dramatic transition to become mature, motile sperm. Because the sperm nucleus is transcriptionally silent, this transition does not involve transcriptional changes. Although Caenorhabditis elegans is a leading model for studies of sperm activation, the mechanisms by which signaling pathways induce this transformation remain poorly characterized. Here we show that a conserved transmembrane zinc transporter, ZIPT-7...
June 2018: PLoS Biology
(no author information available yet)
[This retracts the article on p. 7640 in vol. 8, PMID: 26261684.].
2018: International Journal of Clinical and Experimental Pathology
Timothy P O'Leary, Ahmed T Hussin, Rhian K Gunn, Richard E Brown
The APPswe/PS1dE9 mouse (line 85) is a double transgenic model of Alzheimer's disease (AD) with familial amyloid precursor protein and presenilin-1 mutations. These mice develop age-related behavioral changes reflective of the neuro-psychiatric symptoms (altered anxiety-like behaviour, hyperactivity) and cognitive dysfunction (impaired learning and memory) observed in AD. The APPswe/PS1dE9 mouse has been used to examine the efficacy of therapeutic interventions on behaviour, despite previous difficulties in replicating behavioural phenotypes...
June 2, 2018: Brain Research Bulletin
Ting Cao, Xiaojuan Zhou, Xianjie Zheng, Yue Cui, Joe Z Tsien, Chunxia Li, Huimin Wang
Histone acetylation has been shown to play a crucial role in memory formation, and histone deacetylase (HDAC) inhibitor sodium butyrate (NaB) has been demonstrated to improve memory performance and rescue the neurodegeneration of several Alzheimer's Disease (AD) mouse models. The forebrain presenilin-1 and presenilin-2 conditional double knockout (cDKO) mice showed memory impairment, forebrain degeneration, tau hyperphosphorylation and inflammation that closely mimics AD-like phenotypes. In this article, we have investigated the effects of systemic administration of NaB on neurodegenerative phenotypes in cDKO mice...
2018: Frontiers in Aging Neuroscience
Elisabet Barbero-Camps, Vicente Roca-Agujetas, Isabel Bartolessis, Cristina de Dios, Jose C Fernández-Checa, Montserrat Marí, Albert Morales, Tobias Hartmann, Anna Colell
Macroautophagy/autophagy failure with the accumulation of autophagosomes is an early neuropathological feature of Alzheimer disease (AD) that directly affects amyloid beta (Aβ) metabolism. Although loss of presenilin 1 function has been reported to impair lysosomal function and prevent autophagy flux, the detailed mechanism leading to autophagy dysfunction in AD remains to be elucidated. The resemblance between pathological hallmarks of AD and Niemann-Pick Type C disease, including endosome-lysosome abnormalities and impaired autophagy, suggests cholesterol accumulation as a common link...
June 4, 2018: Autophagy
R Scott Duncan, Bob Song, Peter Koulen
A major cause underlying familial Alzheimer's disease (AD) are mutations in presenilin proteins, presenilin 1 (PS1) and presenilin 2 (PS2). Presenilins are components of the γ-secretase complex which, when mutated, can affect amyloid precursor protein (APP) processing to toxic forms of amyloid beta (Aβ). Consequently, presenilins have been the target of numerous and varied research efforts to develop therapeutic strategies for AD. The presenilin 1 gene harbors the largest number of AD-causing mutations resulting in the late onset familial form of AD...
May 31, 2018: International Journal of Molecular Sciences
Jessyka Maria de França Bram, Leda Leme Talib, Helena Passarelli Giroud Joaquim, Tamires Alves Sarno, Wagner Farid Gattaz, Orestes Vicente Forlenza
The clinical diagnosis of Alzheimer's disease (AD) is a probabilistic formulation that may lack accuracy particularly at early stages of the dementing process. Abnormalities in amyloid-beta precursor protein (APP) metabolism and in the level of APP secretases have been demonstrated in platelets, and to a lesser extent in leukocytes, of AD patients, with conflicting results. The aim of the present study was to compare the protein level of the APP secretases A-disintegrin and metalloprotease 10 (ADAM10), Beta-site APP-cleaving enzyme 1 (BACE1), and presenilin-1 (PSEN1) in platelets and leukocytes from 20 non-medicated older adults with AD and 20 healthy elders, and to determine the potential use of these biomarkers to discriminate cases of AD from controls...
May 29, 2018: European Archives of Psychiatry and Clinical Neuroscience
Rupkatha Banerjee, Zoe Rudloff, Crystal Naylor, Michael Yu, Shermali Gunawardena
Neurons require intracellular transport of essential components for function and viability, and defects in transport has been implicated in many neurodegenerative diseases including Alzheimer's disease (AD). One possible mechanism by which transport defects could occur is by improper regulation of molecular motors. Previous work showed that reduction of Presenilin (PS) or Glycogen synthase kinase 3 beta (GSK3β) stimulated APP vesicle motility. Excess GSK3β caused transport defects and increased motor binding to membranes, while reduction of PS decreased active GSK3β and motor binding to membranes...
May 22, 2018: Human Molecular Genetics
Mohammad Moniruzzaman, Seiko Ishihara, Mika Nobuhara, Hidekazu Higashide, Satoru Funamoto
γ-Secretase complex, the assembly of nicastrin (NCT), Presenilin (PS), Presenilin Enhancer-2 (PEN-2) and Anterior pharynx defective 1 (Aph-1), catalyzes the cleavage of amyloid precursor protein to generate amyloid-β protein (Aβ), the main culprit of Alzheimer's disease. NCT becomes matured through complex glycosylation and play important role in γ-secretase activity by interacting with catalytic subunit PS. However, the role of NCT glycosylation on γ-secretase activity and substrate specificity is still unknown...
May 19, 2018: Biochemical and Biophysical Research Communications
Vinothkumar G, Krishnakumar S, Sureshkumar, Shivashekar G, Sreedhar S, Preethikrishnan, Dinesh S, Sundaram A, Balakrishnan D, Riya, Venkataraman P
BACKGROUND: Cognitive dysfunction is reported to be a major cause of morbidity in chronic kidney disease (CKD). The senile plaques (SPs) in the brain are one of the most pathophysiological characteristics of cognitive dysfunction and its major constituent amyloid β (Aβ) released from amyloid precursor protein (APP) by β (BACE1) and γ (presenilin 1) secretases . Platelets contain more than 95% of the circulating APP and implicate as a candidate biomarker for cognitive decline. Recombinant human erythropoietin (rHuEPO) is a standard therapy for anemia in CKD and also acts as a neuroprotective agent...
May 14, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Neng-Wei Hu, Grant T Corbett, Steven Moore, Igor Klyubin, Tiernan T O'Malley, Dominic M Walsh, Frederick J Livesey, Michael J Rowan
The early stages of Alzheimer's disease are associated with synaptic dysfunction prior to overt loss of neurons. To identify extracellular molecules that impair synaptic plasticity in the brain, we studied the secretomes of human iPSC-derived neuronal models of Alzheimer's disease. When introduced into the rat brain, secretomes from human neurons with either a presenilin-1 mutation, amyloid precursor protein duplication, or trisomy of chromosome 21 all strongly inhibit hippocampal long-term potentiation. Synaptic dysfunction caused by presenilin-1 mutant and amyloid precusor protein duplication secretomes is mediated by Aβ peptides, whereas trisomy of chromosome 21 (trisomy 21) neuronal secretomes induce dysfunction through extracellular tau...
May 15, 2018: Cell Reports
Abadi Kahsu Gebre, Birhanetensay Masresha Altaye, Tesfay Mehari Atey, Kald Beshir Tuem, Derbew Fikadu Berhe
Renin Angiotensin System (RAS) is a hormonal system that regulates blood pressure and fluid balance through a coordinated action of renal, cardiovascular, and central nervous systems. In addition to its hemodynamic regulatory role, RAS involves in many brain activities, including memory acquisition and consolidation. This review has summarized the involvement of RAS in the pathology of Alzheimer's disease (AD), and the outcomes of treatment with RAS inhibitors. We have discussed the effect of brain RAS in the amyloid plaque (Aβ) deposition, oxidative stress, neuroinflammation, and vascular pathology which are directly and indirectly associated with AD...
2018: Frontiers in Pharmacology
Ying Du, Yingjun Zhao, Chuan Li, Qiuyang Zheng, Jing Tian, Zhuyi Li, Timothy Y Huang, Wei Zhang, Huaxi Xu
β-amyloid protein (Aβ) plays a central role in the pathogenesis of Alzheimer disease (AD). Aβ is generated from sequential cleavage of amyloid precursor protein (APP) by β-site APP-cleaving enzyme 1 (BACE1) and the γ-secretase complex. Although activation of some protein kinase C (PKC) isoforms such as PKCα and ε has been shown to regulate nonamyloidogenic pathways and Aβ degradation, it is unclear whether other PKC isoforms are involved in APP processing/AD pathogenesis. In this study, we report that increased PKCδ levels correlate with BACE1 expression in the AD brain...
May 8, 2018: Journal of Experimental Medicine
Mao Huang, Weiwei Qi, Shuhuan Fang, Ping Jiang, Cong Yang, Yousheng Mo, Chang Dong, Yan Li, Jun Zhong, Weibin Cai, Zhonghan Yang, Ti Zhou, Qi Wang, Xia Yang, Guoquan Gao
Alzheimer's disease (AD) is the most common cause of dementia. Pigment epithelium-derived factor (PEDF), a unique neurotrophic protein, decreases with aging. Previous reports have conflicted regarding whether the PEDF concentration is altered in AD patients. In addition, the effect of PEDF on AD has not been documented. Here, we tested serum samples of 31 AD patients and 271 normal controls. We found that compared to PEDF levels in young and middle-aged control subjects, PEDF levels were reduced in old-aged controls and even more so in AD patients...
May 7, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Tomomi Kiyota, Jatin Machhi, Yaman Lu, Bhagyalaxmi Dyavarshetty, Maryam Nemati, Gang Zhang, R Lee Mosley, Harris A Gelbard, Howard E Gendelman
BACKGROUND: The mixed lineage kinase type 3 inhibitor URMC-099 facilitates amyloid-beta (Aβ) clearance and degradation in cultured murine microglia. One putative mechanism is an effect of URMC-099 on Aβ uptake and degradation. As URMC-099 promotes endolysosomal protein trafficking and reduces Aβ microglial pro-inflammatory activities, we assessed whether these responses affect Aβ pathobiogenesis. To this end, URMC-099's therapeutic potential, in Aβ precursor protein/presenilin-1 (APP/PS1) double-transgenic mice, was investigated in this model of Alzheimer's disease (AD)...
May 5, 2018: Journal of Neuroinflammation
Adele Woodhouse, Carmen Maria Fernandez-Martos, Rachel Alice Kathryn Atkinson, Kelsey Anne Hanson, Jessica Marie Collins, Aidan Ryan O'Mara, Nico Terblanche, Marcus Welby Skinner, James Clement Vickers, Anna Elizabeth King
BACKGROUND: There is increasing interest in whether anesthetic agents affect the risk or progression of Alzheimer's disease (AD). To mitigate many of the methodological issues encountered in human retrospective cohort studies we have used a transgenic model of AD to investigate the effect of propofol on AD pathology. METHODS: Six month-old amyloid precursor protein/presenilin 1 (APP/PS1) transgenic AD mice and control mice were exposed to 3 doses of propofol (200 mg/kg) or vehicle, delivered at monthly intervals...
April 25, 2018: BMC Anesthesiology
Alexandre Androuin, Brigitte Potier, U Valentin Nägerl, Daniel Cattaert, Lydia Danglot, Manon Thierry, Ihsen Youssef, Antoine Triller, Charles Duyckaerts, Khalid Hamid El Hachimi, Patrick Dutar, Benoît Delatour, Serge Marty
Alzheimer's disease (AD) is associated with a progressive loss of synapses and neurons. Studies in animal models indicate that morphological alterations of dendritic spines precede synapse loss, increasing the proportion of large and short ("stubby") spines. Whether similar alterations occur in human patients, and what their functional consequences could be, is not known. We analyzed biopsies from AD patients and APP x presenilin 1 knock-in mice that were previously shown to present a loss of pyramidal neurons in the CA1 area of the hippocampus...
April 25, 2018: Acta Neuropathologica
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