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Emma M Perkins, Yvonne L Clarkson, Daumante Suminaite, Alastair R Lyndon, Kohichi Tanaka, Jeffrey D Rothstein, Paul Skehel, David J A Wyllie, Mandy Jackson
Loss of excitatory amino acid transporters (EAATs) has been implicated in a number of human diseases including spinocerebellar ataxias, Alzhiemer's disease and motor neuron disease. EAAT4 and GLAST/EAAT1 are the two predominant EAATs responsible for maintaining low extracellular glutamate levels and preventing neurotoxicity in the cerebellum, the brain region essential for motor control. Here using genetically modified mice we identify new critical roles for EAAT4 and GLAST/EAAT1 as modulators of Purkinje cell (PC) spontaneous firing patterns...
May 8, 2018: Human Molecular Genetics
Neeraj Rastogi, Nidhi Tyagi, Ovender Singh, B S Hemanth Kumar, Udai P Singh, Kaushik Ghosh, Raja Roy
We report the synthesis and characterization of manganese(II) complexes having pentadentate ligands L1 (2,6-bis(1-(2-phenyl-2-(pyridin-2-yl)hydrazono)ethyl)pyridine), L2 (methyl 2,6-bis((E)-1-(2-phenyl-2-(pyridin-2yl)hydrazono)ethyl)isonicotinate), L3 (N-(2-(1H-indol-3-yl)ethyl)-2,6-bis((E)-1-(2-phenyl-2-(pyridin2yl)hydrazono)ethyl)isonicotiamide) and their application as dual contrast agents for simultaneous T1 and T2 weighted magnetic resonance imaging. Single crystal analysis of all the complexes [MnII L1 , MnII L2 and MnII L3 ] confirm the formation of novel seven-coordinate manganese complexes with an inner sphere water and perchlorate ion...
December 2017: Journal of Inorganic Biochemistry
Selva Ganapathy Velayutham, Sadanandavalli Retnaswami Chandra, Srikala Bharath, Ravi Girikamatha Shankar
INTRODUCTION: Alzhiemers disease and Frontotemporal dementia are common neurodegenerative dementias with a wide prevalence. Falls are a common cause of morbidity in these patients. Identifying subclinical involvement of these parameters might serve as a tool in differential analysis of these distinct parameters involved in these conditions and also help in planning preventive strategies to prevent falls. PATIENTS AND METHODS: Eight patients in age and gender matched patients in each group were compared with normal controls...
March 2017: Indian Journal of Psychological Medicine
Linh Q Lam, Bruce X Wong, Tony Frugier, Qiao-Xin Li, Steven J Collins, Ashley I Bush, Peter J Crack, James A Duce
Ferroxidase activity has been reported to be altered in various biological fluids in neurodegenerative disease, but the sources contributing to the altered activity are uncertain. Here we assay fractions of serum and cerebrospinal fluid with a newly validated triplex ferroxidase assay. Our data indicate that while ceruloplasmin, a multicopper ferroxidase, is the predominant source of serum activity, activity in CSF predominantly derives from a <10 kDa component, specifically from polyanions such as citrate and phosphate...
April 19, 2017: ACS Chemical Neuroscience
Nuggehally R Srinivas
PURPOSE: Although an optimized delivery of rivastigmine for management of Alzhiemer disease (AD) is provided by the transdermal patch, it is critical to establish a limited sampling strategy for the measurement of exposure of rivastigmine/NAP226-90. METHODS: The relationship Cmax versus AUC0-24h for rivastigmine/NAP226-90 was established by regression models. The derived regression equations enabled the prediction AUC0-24h for rivastigmine and NAP226-90. Models were evaluated using statistical criteria...
July 2016: Clinical Neuropharmacology
David Douglas, Maged Goubran, Eugene Wilson, Guofan Xu, Pragya Tripathi, Dawn Holley, Steven Chao, Max Wintermark, Andrew Quon, Michael Zeineh, Minal Vasanawala, Greg Zaharchuk
No abstract text is available yet for this article.
December 2015: EJNMMI Physics
James A Hebda, Mazin Magzoub, Andrew D Miranker
Islet Amyloid Polypeptide (IAPP) is a 37-residue hormone cosecreted with insulin by the β-cells of the pancreas. Amyloid fiber aggregation of IAPP has been correlated with the dysfunction and death of these cells in type II diabetics. The likely mechanisms by which IAPP gains toxic function include energy independent cell membrane penetration and induction of membrane depolarization. These processes have been correlated with solution biophysical observations of lipid bilayer catalyzed acceleration of amyloid formation...
October 2014: Protein Science: a Publication of the Protein Society
Zheng Wu, Ziyuan Guo, Marla Gearing, Gong Chen
Amyloid plaques and tau tangles are common pathological hallmarks for Alzheimer's disease (AD); however, reducing Aβ production failed to relieve the symptoms of AD patients. Here we report a high GABA (γ-aminobutyric acid) content in reactive astrocytes in the dentate gyrus (DG) of a mouse model for AD (5xFAD) that results in increased tonic inhibition and memory deficit. We also confirm in human AD patient brains that dentate astrocytes have a high GABA content, suggesting that high astrocytic GABA level may be a novel biomarker and a potential diagnostic tool for AD...
2014: Nature Communications
Pradip K Kamat, Shivika Rai, Supriya Swarnkar, Rakesh Shukla, Chandishwar Nath
Okadaic acid (OKA), a polyether C38 fatty acid toxin extracted from a black sponge Hallichondria okadaii, is a potent and selective inhibitor of protein phosphatase, PP1 and PP2A. OKA has been proved to be a powerful probe for studying the various regulatory mechanisms and neurotoxicity. Because of its property to inhibit phosphatase activity, OKA is associated with protein phosphorylation; it is implicated in hyperphosphorylation of tau and in later stages causes Alzhiemer's disease (AD)-like pathology. AD is a progressive neurodegenerative disorder, pathologically characterized by extracellular amyloid beta (Aβ) plaques and intracellular neurofibrillary tangles (NFTs)...
December 2014: Molecular Neurobiology
Susan M Landau, Mark A Mintun, Abhinay D Joshi, Robert A Koeppe, Ronald C Petersen, Paul S Aisen, Michael W Weiner, William J Jagust
OBJECTIVE: Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) population, we examined (1) cross-sectional relationships between amyloid deposition, hypometabolism, and cognition, and (2) associations between amyloid and hypometabolism measurements and longitudinal cognitive measurements. METHODS: We examined associations between mean cortical florbetapir uptake, mean (18) F-fluorodeoxyglucose-positron emission tomography (FDG-PET) within a set of predefined regions, and Alzhiemer's Disease Assessment Scale (ADAS-cog) performance in 426 ADNI participants (126 normal, 162 early mild cognitive impairment [EMCI], 85 late MCI [LMCI], 53 Alzheimer disease [AD] patients)...
October 2012: Annals of Neurology
Jagat R Kanwar, Xueying Sun, Vasu Punj, Bhasker Sriramoju, Rajiv R Mohan, Shu-Feng Zhou, Ashok Chauhan, Rupinder K Kanwar
UNLABELLED: The incidence of neurological diseases of unknown etiology is increasing, including well-studied diseases such as Alzhiemer's, Parkinson's, and multiple sclerosis. The blood-brain barrier provides protection for the brain but also hinders the treatment and diagnosis of these neurological diseases, because the drugs must cross the blood-brain barrier to reach the lesions. Thus, attention has turned to developing novel and effective delivery systems that are capable of carrying drug and that provide good bioavailability in the brain...
May 2012: Nanomedicine: Nanotechnology, Biology, and Medicine
Xiao-Dong Pan, Yuan-Gui Zhu, Nan Lin, Jing Zhang, Qin-Yong Ye, Hua-Pin Huang, Xiao-Chun Chen
BACKGROUND: Reactive microglia are associated with β-amyloid (Aβ) deposit and clearance in Alzhiemer's Disease (AD). Paradoxically, entocranial resident microglia fail to trigger an effective phagocytic response to clear Aβ deposits although they mainly exist in an "activated" state. Oligomeric Aβ (oAβ), a recent target in the pathogenesis of AD, can induce more potent neurotoxicity when compared with fibrillar Aβ (fAβ). However, the role of the different Aβ forms in microglial phagocytosis, induction of inflammation and oxidation, and subsequent regulation of phagocytic receptor system, remain unclear...
2011: Molecular Neurodegeneration
Al Bartolucci, Sejong Bae, Karan Singh, H Randall Griffith
The mini mental state examination (MMSE) is a common tool for measuring cognitive decline in Alzhiemer's Disease (AD) subjects. Subjects are usually observed for a specified period of time or until death to determine the trajectory of the decline which for the most part appears to be linear. However, it may be noted that the decline may not be modeled by a single linear model over a specified period of time. There may be a point called a change point where the rate or gradient of the decline may change depending on the length of time of observation...
November 2009: Mathematics and Computers in Simulation
G T Grossberg, C Sadowsky, J T Olin
Today patients with mild to moderate Alzhiemer's disease (AD) have a treatment approach choice: oral or transdermal delivery. The aim of this review was to provide a concise, comprehensive overview of the clinically relevant safety, tolerability and efficacy information available for the rivastigmine transdermal system. Relevant articles were identified through a MEDLINE search of publications in the past 3 years using the terms 'rivastigmine' and 'transdermal' or 'patch'. Efficacy, safety and tolerability of the rivastigmine patch vs...
April 2010: International Journal of Clinical Practice
C Dreux
All healthcare professionals are concerned by Alzheimer's disease, which in France will affect, in just a few years, over one million persons, mainly women. Pharmacists have shown particular interest, irrespective of their sector of activity. Here, we wanted to better define the role of colleagues who are constantly in contact with the public, i.e. in France in drug dispensaries and biology laboratories. Within the framework of the French pharmacy committee for health and social education, Cespharm, the Ethics and Communications working group of the 2008-2012 Alzheimer Disease Committee headed by Professor Joël Menard proposed a project worksheet which can be used by French pharmacists in their action to help Alzheimer patients and their caregivers...
March 2009: Annales Pharmaceutiques Françaises
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