Upregulation of glycolytic enzymes, mitochondrial dysfunction and increased cytotoxicity in glial cells treated with Alzheimer's disease plasma

PloS One
Tharusha JayasenaPerminder S Sachdev

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder associated with increased oxidative stress and neuroinflammation. Markers of increased protein, lipid and nucleic acid oxidation and reduced activities of antioxidant enzymes have been reported in AD plasma. Amyloid plaques in the AD brain elicit a range of reactive inflammatory responses including complement activation and acute phase reactions, which may also be reflected in plasma. Previous studies have shown that human AD plasma may be cytotoxic to cultured cells. We investigated the effect of pooled plasma (n = 20 each) from healthy controls, individuals with amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) on cultured microglial cells. AD plasma and was found to significantly decrease cell viability and increase glycolytic flux in microglia compared to plasma from healthy controls. This effect was prevented by the heat inactivation of complement. Proteomic methods and isobaric tags (iTRAQ) found the expression level of complement and other acute phase proteins to be altered in MCI and AD plasma and an upregulation of key enzymes involved in the glycolysis pathway in cells exposed to AD plasma. Altered expression levels of acute phase reactants ...Continue Reading

References

Nov 1, 1992·Journal of Neuroscience Research·G J Brewer, J W Ashford
Nov 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·J RogersP Ward
Nov 9, 1992·Neuroscience Letters·H AkiyamaP L McGeer
Mar 1, 1991·Neurology·J E HamosD A Drachman
May 28, 1990·Brain Research·T C RuijsJ P Antel
Nov 1, 1989·The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques·H F BradfordJ Hardy
Jun 1, 1973·Analytical Biochemistry·C Bernofsky, M Swan
Jan 1, 1981·Journal of Toxicology and Environmental Health·D B Mitchell, D Acosta
Jan 1, 1995·Critical Reviews in Oral Biology and Medicine : an Official Publication of the American Association of Oral Biologists·S R Barnum
Feb 1, 1993·Neuropathology and Applied Neurobiology·P J HarrisonR C Pearson
Feb 1, 1997·Trends in Biochemical Sciences·S TsukitaS Tsukita
Jun 17, 1998·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·W J PowersT O Videen
Aug 7, 1998·Neurochemistry International·F M de GannesP J Voisin
Mar 11, 1999·Annals of Neurology·J L Price, J C Morris
Mar 18, 1999·The American Journal of Pathology·K YasojimaP L McGeer
Aug 12, 1999·Journal of Neural Transmission·M BiglK Eschrich
Jun 19, 2001·Neuroscience Letters·Y ShenJ Rogers
Aug 31, 2001·QJM : Monthly Journal of the Association of Physicians·L T McGrathA P Passmore
Jan 5, 2002·International Psychogeriatrics·J A O'Brien, J J Caro
Apr 26, 2002·Neuroreport·Pia DavidssonKaj Blennow
Jun 6, 2002·The Journal of Dairy Research·Pascal Rainard
Jun 12, 2002·Archives of Neurology·Domenico PraticòJohn Q Trojanowski
Oct 16, 2003·Brain Research. Molecular Brain Research·Maja PuchadesPia Davidsson
Oct 22, 2003·Progress in Neurobiology·Yong Shen, Seppo Meri
Nov 5, 2003·Proteomics·Han-Ling YuHyman M Schipper
Jan 20, 2004·Proteomics·Rulin ZhangGeorge Jackowski
Feb 11, 2004·Proceedings of the National Academy of Sciences of the United States of America·Eric M BlalockPhilip W Landfield

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Citations

Jun 9, 2016·Scientific Reports·Haochen LiuUNKNOWN Alzheimer’s Disease Neuroimaging Initiative
Dec 3, 2016·Biochemistry. Biokhimii︠a︡·S S KudryavtsevaV I Muronetz
May 16, 2020·Oxidative Medicine and Cellular Longevity·Alyne Mendonça Marques TonElisardo Corral Vasquez
Apr 14, 2017·Metabolic Brain Disease·Olayemi Joseph OlajideChristiana Bidemi Oyegbola
Sep 14, 2017·Frontiers in Aging Neuroscience·Justin CohenClaudio Torres
Mar 18, 2019·Journal of Molecular Biology·Blanca I Aldana
May 18, 2021·Frontiers in Neuroscience·Xin ZhangLiqin Zhao

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Methods Mentioned

BETA
protein assay
electrophoresis
transgenic
metabolomic profiling

Software Mentioned

MassLynx
Mass Measure
Scaffold
Protein Pilot
ProteinProphet
Proteome
STRING
Excel
Scaffold Q +
Mascot

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