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https://www.readbyqxmd.com/read/29352484/melatonin-ameliorates-a%C3%AE-42-induced-alteration-of-%C3%AE-app-processing-secretases-via-the-melatonin-receptor-through-the-pin1-gsk3%C3%AE-nf-%C3%AE%C2%BAb-pathway-in-sh-sy5y-cells
#1
Vorapin Chinchalongporn, Mayuri Shukla, Piyarat Govitrapong
Melatonin is involved in the physiological regulation of the β- amyloid precursor protein (βAPP) cleaving secretases which are responsible for generation of the neurotoxic amyloid beta (Aβ) peptide, one of the hallmarks of Alzheimer's disease (AD) pathology. In this study, we aimed to determine the underlying mechanisms of this regulation under pathological conditions. We establish that melatonin prevents Aβ42 -induced down-regulation of a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) as well as up-regulation of β-site APP-cleaving enzyme 1 (BACE1) and presenilin 1 (PS1) in SH-SY5Y cell cultures...
January 20, 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29346315/dietary-total-prenylflavonoids-from-the-fruits-of-psoralea-corylifolia-l-prevents-age-related-cognitive-deficits-and-down-regulates-alzheimer-s-markers-in-samp8-mice
#2
Zhi-Jing Chen, Yan-Fang Yang, Ying-Tao Zhang, Dong-Hui Yang
Alzheimer's disease (AD) is a serious threat for the aging society. In this study, we examined the preventive effect of the total prenylflavonoids (TPFB) prepared from the dried fruits of Psoralea corylifolia L., using an age-related AD mouse model SAMP8. We found that long-term dietary TPFB at 50 mg/kg·day significantly improved cognitive performance of the SAMP8 mice in Morris water maze tests, similar to 150 mg/kg·day of resveratrol, a popular neuro-protective compound. Furthermore, TPFB treatment showed significant improvements in various AD markers in SAMP8 brains, which were restored to near control levels of the normal mice, SAMR1...
January 18, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29346139/blood-biomarkers-for-evaluation-of-perinatal-encephalopathy-state-of-the-art
#3
Ernest M Graham, Allen D Everett, Jean-Christophe Delpech, Frances J Northington
PURPOSE OF REVIEW: The rapid progress in biomarker science is on the threshold of significantly changing clinical care for infants in the neonatal ICU. Infants with neonatal brain injuries will likely be the first group whose management is dramatically altered with point-of-care, rapidly available brain biomarker analysis. Providing an interim update on progress in this area is the purpose of this review. RECENT FINDINGS: Highlighted findings from the past 18 months of publications on biomarkers in neonatal brain injury include; Specific nonbrain markers of cardiac health and global asphyxia continue to provide information on brain injury after hypoxic-ischemic encephalopathy (HIE)...
January 17, 2018: Current Opinion in Pediatrics
https://www.readbyqxmd.com/read/29346009/automation-on-an-open-access-platform-of-alzheimer-s-disease-biomarker-immunoassays
#4
Benjamin Gille, Lieselot Dedeene, Erik Stoops, Leentje Demeyer, Cindy Francois, Stefanie Lefever, Maxim De Schaepdryver, Britta Brix, Rik Vandenberghe, Jos Tournoy, Hugo Vanderstichele, Koen Poesen
The lack of (inter-)laboratory standardization has hampered the application of universal cutoff values for Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers and their transfer to general clinical practice. The automation of the AD biomarker immunoassays is suggested to generate more robust results than using manual testing. Open-access platforms will facilitate the integration of automation for novel biomarkers, allowing the introduction of the protein profiling concept. A feasibility study was performed on an automated open-access platform of the commercial immunoassays for the 42-amino-acid isoform of amyloid-β (Aβ1-42), Aβ1-40, and total tau in CSF...
January 1, 2018: SLAS Technology
https://www.readbyqxmd.com/read/29345897/design-synthesis-and-biological-evaluation-of-1-benzylamino-2-hydroxyalkyl-derivatives-as-new-potential-disease-modifying-multifunctional-anti-alzheimer-s-agents
#5
Dawid Panek, Anna Więckowska, Jakub Jończyk, Justyna Godyń, Marek W Bajda, Tomasz Wichur, Anna Pasieka, Damijan Knez, Anja Pislar, Jan Korabecny, Ondrej Soukup, Vendula Sepsova, Raimon Sabaté, Janko Kos, Stanislav Gobec, Barbara Malawska
The multitarget approach is a promising paradigm in drug discovery, potentially leading to new treatment options for complex disorders, such as Alzheimer's disease. Herein, we present the discovery of a unique series of 1-benzylamino-2-hydroxyalkyl derivatives combining inhibitory activity against butyrylcholinesterase, β-secretase, β-amyloid and tau protein aggregation, all related to mechanisms which underpin Alzheimer's disease. Notably, diphenylpropylamine derivative 10 showed balanced activity against both disease-modifying targets - inhibition of β-secretase (IC50 hBACE-1 = 41...
January 18, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29341269/characterization-of-a-3xtg-ad-mouse-model-of-alzheimer-s-disease-with-the-senescence-accelerated-mouse-prone-8-samp8-background
#6
Jessica Virgili, Meryem Lebbadi, Cyntia Tremblay, Isabelle St-Amour, Caroline Pierrisnard, Audrey Faucher-Genest, Vincent Emond, Carl Julien, Frédéric Calon
No model fully recapitulates the neuropathology of Alzheimer's disease (AD). Although the triple-transgenic mouse model of AD (3xTg-AD) expresses Aβ plaques and tau-laden neurofibrillary tangles, as well as synaptic and behavioral deficits, it does not display frank neuronal loss. Since old age is the most important risk factor in AD, senescence-related interactions might be lacking to truly establish an AD-like environment. To investigate this hypothesis, we bred the 3xTg-AD mouse with the senescence-accelerated mouse prone 8 (SAMP8), a model of accelerated aging...
January 17, 2018: Synapse
https://www.readbyqxmd.com/read/29341130/mitochondrial-function-and-autophagy-integrating-proteotoxic-redox-and-metabolic-stress-in-parkinson-s-disease
#7
REVIEW
Jianhua Zhang, M Lillian Culp, Jason G Craver, Victor Darley-Usmar
Parkinson's disease (PD) is a movement disorder with widespread neurodegeneration in the brain. Significant oxidative, reductive, metabolic, and proteotoxic alterations have been observed in PD postmortem brains. The alterations of mitochondrial function resulting in decreased bioenergetic health is important and needs to be further examined to help develop biomarkers for PD severity and prognosis. It is now becoming clear that multiple hits on metabolic and signaling pathways are likely to exacerbate PD pathogenesis...
January 17, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29338754/molecular-and-functional-signatures-in-a-novel-alzheimer-s-disease-mouse-model-assessed-by-quantitative-proteomics
#8
Dong Kyu Kim, Joonho Park, Dohyun Han, Jinhee Yang, Ahbin Kim, Jongmin Woo, Youngsoo Kim, Inhee Mook-Jung
BACKGROUND: Alzheimer's disease (AD), the most common neurodegenerative disorder, is characterized by the deposition of extracellular amyloid plaques and intracellular neurofibrillary tangles. To understand the pathological mechanisms underlying AD, developing animal models that completely encompass the main features of AD pathologies is indispensable. Although mouse models that display pathological hallmarks of AD (amyloid plaques, neurofibrillary tangles, or both) have been developed and investigated, a systematic approach for understanding the molecular characteristics of AD mouse models is lacking...
January 16, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29338678/supplementation-with-curcuma-longa-reverses-neurotoxic-and-behavioral-damage-in-models-of-alzheimer-s-disease-a-systematic-review
#9
Ianara Mendonca da Costa, Marco Aurelio de Moura Freire, Jose Rodolfo Lopes de Paiva Cavalcanti, Dayane Pessoa de Araujo, Bianca Norrara, Isleania Maria Marques Moreira Rosa, Eduardo Pereira de Azevedo, Amalia Cinthia Meneses do Rego, Irami Araujo Filho, Fausto Pierdona Guzen
BACKGROUND: The formation of senile plaques and neurofibrillary tangles of the tau protein are the main pathological mechanism of Alzheimer's disease (AD). Current therapies for AD offer discrete benefits to the clinical symptoms and do not prevent the continuing degeneration of neuronal cells. Therefore, novel therapeutic strategies have long been investigated, where curcumin (Curcuma longa) has shown some properties that can prevent the deleterious processes involved in neurodegenerative diseases...
January 16, 2018: Current Neuropharmacology
https://www.readbyqxmd.com/read/29338612/gene-profiling-of-nucleus-basalis-tau-containing-neurons-in-chronic-traumatic-encephalopathy-a-chronic-effects-of-neurotrauma-consortium-study
#10
Elliott Jay Mufson, Bin He, Stephen D Ginsberg, Benjamin A Carper, Gayle S Bieler, Fiona C Crawford, Victor E Alverez, Bernard R Huber, Thor D Stein, Ann C McKee, Sylvia E Perez
Military personnel and athletes exposed to traumatic brain injury may develop chronic traumatic encephalopathy (CTE). Brain pathology in CTE includes intracellular accumulation of abnormally phosphorylated tau proteins (p-tau), the main constituent of neurofibrillary tangles (NFTs). Recently, we found that cholinergic basal forebrain (CBF) neurons within the nucleus basalis of Meynert (nbM), which provide the major cholinergic innervation to the cortex, display an increasing number of NFTs across the pathological stages of CTE...
January 16, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29338452/an-update-on-diagnostic-and-prognostic-biomarkers-for-traumatic-brain-injury
#11
Kevin K Wang, Zhihui Yang, Tian Zhu, Yuan Shi, Richard Rubenstein, J Adrian Tyndall, Geoff T Manley
Traumatic brain injury (TBI) is a major worldwide neurological disorder of epidemic proportions. To date, there are still no FDA-approved therapies to treat any forms of TBI. Encouragingly, there are emerging data showing that biofluid-based TBI biomarker tests have the potential to diagnose the presence of TBI of different severities including concussion, and to predict outcome. Area covered: The authors provide an update on the current knowledge of TBI biomarkers, including protein biomarkers for neuronal cell body injury (UCH-L1, NSE), astroglial injury (GFAP, S100B), neuronal cell death (αII-spectrin breakdown products), axonal injury (NF proteins), white matter injury (MBP), post-injury neurodegeneration (total Tau and phospho-Tau), post-injury autoimmune response (brain antigen-targeting autoantibodies), and other emerging non-protein biomarkers...
January 17, 2018: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/29337233/tau-deficiency-down-regulated-transcription-factor-orthodenticle-homeobox-2-expression-in-the-dopaminergic-neurons-in-ventral-tegmental-area-and-caused-no-obvious-motor-deficits-in-mice
#12
Xiaolu Tang, Luyan Jiao, Meige Zheng, Yan Yan, Qi Nie, Ting Wu, Xiaomei Wan, Guofeng Zhang, Yonglin Li, Song Wu, Bin Jiang, Huaibin Cai, Pingyi Xu, Jinhai Duan, Xian Lin
Tau protein participates in microtubule stabilization, axonal transport, and protein trafficking. Loss of normal tau function will exert a negative effect. However, current knowledge on the impact of tau deficiency on the motor behavior and related neurobiological changes are controversial. In this study, we examined motor functions and analyzed several proteins implicated in the maintenance of midbrain dopaminergic (DA) neurons (mDANs) function of adult and aged tau+/+, tau+/-, tau-/- mice. We found tau deficiency could not induce significant motor disorders...
January 11, 2018: Neuroscience
https://www.readbyqxmd.com/read/29332046/a-novel-antibody-targeting-tau-phosphorylated-at-serine-235-detects-neurofibrillary-tangles
#13
David Brici, Jürgen Götz, Rebecca M Nisbet
Alzheimer's disease is characterized by two main pathological hallmarks in the human brain: the extracellular deposition of amyloid-β as plaques and the intracellular accumulation of the hyperphosphorylated protein tau as neurofibrillary tangles (NFTs). Phosphorylated tau (p-tau) specific-antibodies and silver staining have been used to reveal three morphological stages of NFT formation: pre-NFTs, intraneuronal NFTs (iNFTs), and extraneuronal NFTs (eNFTs). Here we characterize a novel monoclonal antibody, RN235, which is specific for tau phosphorylated at serine 235, and detects iNFTs and eNFTs in brain tissue, suggesting that phosphorylation at this site is indicative of late stage changes in tau...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29332041/in-vivo-visualization-of-tau-accumulation-microglial-activation-and-brain-atrophy-in-a-mouse-model-of-tauopathy-rtg4510
#14
Ai Ishikawa, Masaki Tokunaga, Jun Maeda, Takeharu Minamihisamatsu, Masafumi Shimojo, Hiroyuki Takuwa, Maiko Ono, Ruiqing Ni, Shigeki Hirano, Satoshi Kuwabara, Bin Ji, Ming-Rong Zhang, Ichio Aoki, Tetsuya Suhara, Makoto Higuchi, Naruhiko Sahara
BACKGROUND: Tau imaging using PET is a promising tool for the diagnosis and evaluation of tau-related neurodegenerative disorders, but the relationship among PET-detectable tau, neuroinflammation, and neurodegeneration is not yet fully understood. OBJECTIVE: We aimed to elucidate sequential changes in tau accumulation, neuroinflammation, and brain atrophy by PET and MRI in a tauopathy mouse model. METHODS: rTg4510 transgenic (tg) mice expressing P301L mutated tau and non-tg mice were examined with brain MRI and PET imaging (analyzed numbers: tg = 17, non-tg = 13; age 2...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29331876/app-go-protein-g%C3%AE-%C3%AE-complex-signaling-mediates-a%C3%AE-degeneration-and-cognitive-impairment-in-alzheimer-s-disease-models
#15
Elena Anahi Bignante, Nicolás Eric Ponce, Florencia Heredia, Juliana Musso, María C Krawczyk, Julieta Millán, Gustavo F Pigino, Nibaldo C Inestrosa, Mariano M Boccia, Alfredo Lorenzo
Deposition of amyloid-β (Aβ), the proteolytic product of the amyloid precursor protein (APP), might cause neurodegeneration and cognitive decline in Alzheimer's disease (AD). However, the direct involvement of APP in the mechanism of Aβ-induced degeneration in AD remains on debate. Here, we analyzed the interaction of APP with heterotrimeric Go protein in primary hippocampal cultures and found that Aβ deposition dramatically enhanced APP-Go protein interaction in dystrophic neurites. APP overexpression rendered neurons vulnerable to Aβ toxicity by a mechanism that required Go-Gβγ complex signaling and p38-mitogen-activated protein kinase activation...
December 20, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/29331845/effect-of-levetiracetam-on-extracellular-amino-acid-levels-in-the-dorsal-hippocampus-of-rats-with-temporal-lobe-epilepsy
#16
Pichardo Macías Luz Adriana, Ramírez Mendiola Blanca Alcira, Contreras García Itzel Jatziri, Zamudio Hernández Sergio Roberto, Chávez Pacheco Juan Luis, Sánchez Huerta Karla Berenice, Mendoza Torreblanca Julieta Griselda
Levetiracetam (LEV) is an anticonvulsant drug with a unique mechanism of action that is not completely understood. However, its activity profile may involve effects on excitatory and/or inhibitory neurotransmission since the primary target of LEV, synaptic vesicle protein 2A, is ubiquitously expressed in all types of synaptic vesicles. Therefore, the objective of the present study was to explore the effect of LEV (300 mg/kg/day for one week, administered via osmotic mini-pumps) on neurotransmitter release and its probable selective effect on extracellular gamma-amino butyric acid (GABA), glutamate (Glu), aspartate (Asp), glutamine (Gln), taurine (Tau) and glycine (Gly) concentrations (using in vivo microdialysis under basal and high-K+ conditions) in the dorsal hippocampus (DH), a region that undergoes major synaptic changes during epilepsy...
January 5, 2018: Epilepsy Research
https://www.readbyqxmd.com/read/29331531/profiles-of-%C3%AE-amyloid-peptides-and-key-secretases-in-brain-autopsy-samples-differ-with-sex-and-apoe-%C3%AE%C2%B54-status-impact-for-risk-and-progression-of-alzheimer-disease
#17
Jennifer N K Nyarko, Maa O Quartey, Paul R Pennington, Ryan M Heistad, Doris Dea, Judes Poirier, Glen B Baker, Darrell D Mousseau
The APOE ε 4 allele was originally reported to contribute to risk of Alzheimer disease (AD) in women, yet male and female AD patient-derived data are routinely pooled. Histopathological hallmarks of AD include neurofibrillary tangles centered on hyperphosphorylated Tau and plaques composed of the β -amyloid (A β) peptide that is derived by sequential secretase-mediated cleavage of the Amyloid Protein Precursor (APP). We chose to examine profiles of A β (1-40), A β (1-42), and N-truncated (i.e. p3-related) fragments in the plaque-associated fraction of autopsied cortical and corresponding hippocampal samples from donors with a diagnosis of early-onset (EOAD) and late-onset (LOAD) AD...
January 10, 2018: Neuroscience
https://www.readbyqxmd.com/read/29328927/alzheimer-s-disease-biomarker-guided-diagnostic-workflow-using-the-added-value-of-six-combined-cerebrospinal-fluid-candidates-a%C3%AE-1-42-total-tau-phosphorylated-tau-nfl-neurogranin-and-ykl-40
#18
Harald Hampel, Nicola Toschi, Filippo Baldacci, Henrik Zetterberg, Kaj Blennow, Ingo Kilimann, Stefan J Teipel, Enrica Cavedo, Antonio Melo Dos Santos, Stéphane Epelbaum, Foudil Lamari, Remy Genthon, Bruno Dubois, Roberto Floris, Francesco Garaci, Simone Lista
INTRODUCTION: The diagnostic and classificatory performances of all combinations of three core (amyloid β peptide [i.e., Aβ1-42], total tau [t-tau], and phosphorylated tau) and three novel (neurofilament light chain protein, neurogranin, and YKL-40) cerebrospinal fluid biomarkers of neurodegeneration were compared among individuals with mild cognitive impairment (n = 41), Alzheimer's disease dementia (ADD; n = 35), frontotemporal dementia (FTD; n = 9), and cognitively healthy controls (HC; n = 21), using 10-fold cross-validation...
January 9, 2018: Alzheimer's & Dementia: the Journal of the Alzheimer's Association
https://www.readbyqxmd.com/read/29328367/tumorigenic-proteins-upregulated-in-the-mycn-amplified-imr-32-human-neuroblastoma-cells-promote-proliferation-and-migration
#19
Hayat Zaatiti, Jad Abdallah, Zeina Nasr, George Khazen, Anthony Sandler, Tamara J Abou-Antoun
Childhood neuroblastoma is one of the most common types of extra-cranial cancer affecting children with a clinical spectrum ranging from spontaneous regression to malignant and fatal progression. In order to improve the clinical outcomes of children with high-risk neuroblastoma, it is crucial to understand the tumorigenic mechanisms that govern its malignant behaviors. MYCN proto-oncogene, bHLH transcription factor (MYCN) amplification has been implicated in the malignant, treatment-evasive nature of aggressive, high-risk neuroblastoma...
January 4, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29327503/noncoding-rnas-in-alzheimer-s-disease
#20
REVIEW
M Laura Idda, Rachel Munk, Kotb Abdelmohsen, Myriam Gorospe
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the main cause of dementia among the elderly worldwide. Despite intense efforts to develop drugs for preventing and treating AD, no effective therapies are available as yet, posing a growing burden at the personal, medical, and socioeconomic levels. AD is characterized by the production and aggregation of amyloid β (Aβ) peptides derived from amyloid precursor protein (APP), the presence of hyperphosphorylated microtubule-associated protein Tau (MAPT), and chronic inflammation leading to neuronal loss...
January 12, 2018: Wiley Interdisciplinary Reviews. RNA
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