title: Macrophage Migration Inhibitory Factor is subjected to glucose modification and oxidation in Alzheimer's Disease.
abstract: Glucose and glucose metabolites are able to adversely modify proteins through a non-enzymatic reaction called glycation, which is associated with the pathology of Alzheimer's Disease (AD) and is a characteristic of the hyperglycaemia induced by diabetes. However, the precise protein glycation profile that characterises AD is poorly defined and the molecular link between hyperglycaemia and AD is unknown. In this study, we define an early glycation profile of human brain using fluorescent phenylboronate gel electrophoresis and identify early glycation and oxidation of macrophage migration inhibitory factor (MIF) in AD brain. This modification inhibits MIF enzyme activity and ability to stimulate glial cells. MIF is involved in immune response and insulin regulation, hyperglycaemia, oxidative stress and glycation are all implicated in AD. Our study indicates that glucose modified and oxidised MIF could be a molecular link between hyperglycaemia and the dysregulation of the innate immune system in AD.
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, U.K.
authors.forename: Omar
authors.initials: O
authors.lastname: Kassaar
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, U.K.
authors.forename: Marta
authors.initials: M
authors.lastname: Pereira Morais
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, U.K.
authors.forename: Suying
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, U.K.
authors.forename: Emily L
authors.initials: EL
authors.lastname: Adam
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, U.K.
authors.forename: Rosemary C
authors.initials: RC
authors.lastname: Chamberlain
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, U.K.
authors.forename: Bryony
authors.initials: B
authors.lastname: Jenkins
authors.affiliation: Department of Chemistry, University of Bath, Bath, BA2 7AY, U.K.
authors.forename: Tony D
authors.initials: TD
authors.lastname: James
authors.affiliation: Institute of Psychiatry, Psychology &Neuroscience, Wolfson Centre for Age Related Diseases, King's College London, London, SE1 1UL, U.K.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Francis
authors.affiliation: Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, U.K.
authors.forename: Stephen
authors.initials: S
authors.lastname: Ward
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, U.K.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Williams
authors.affiliation: Department of Biology and Biochemistry, University of Bath, Bath, BA2 7AY, U.K.
authors.forename: Jean
authors.initials: J
authors.lastname: van den Elsen
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism*; D018384:Oxidative Stress
chemical_list: D008263:Macrophage Migration-Inhibitory Factors; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human; D005947:Glucose