Amyloid Plaque-Associated Oxidative Degradation of Uniformly Radiolabeled Arachidonic Acid

ACS Chemical Neuroscience
Ran FurmanPaul H Axelsen

Abstract

Oxidative stress is a frequently observed feature of Alzheimer's disease, but its pathological significance is not understood. To explore the relationship between oxidative stress and amyloid plaques, uniformly radiolabeled arachidonate was introduced into transgenic mouse models of Alzheimer's disease via intracerebroventricular injection. Uniform labeling with carbon-14 is used here for the first time, and made possible meaningful quantification of arachidonate oxidative degradation products. The injected arachidonate entered a fatty acid pool that was subject to oxidative degradation in both transgenic and wild-type animals. However, the extent of its degradation was markedly greater in the hippocampus of transgenic animals where amyloid plaques were abundant. In human Alzheimer's brain, plaque-associated proteins were post-translationally modified by hydroxynonenal, a well-known oxidative degradation product of arachidonate. These results suggest that several recurring themes in Alzheimer's pathogenesis, amyloid β proteins, transition metal ions, oxidative stress, and apolipoprotein isoforms, may be involved in a common mechanism that has the potential to explain both neuronal loss and fibril formation in this disease.

References

Apr 1, 1974·British Journal of Pharmacology·G G Shaw
Aug 1, 1997·Journal of Neuropathology and Experimental Neurology·K S MontineT J Montine
Dec 9, 1997·Neurobiology of Aging·M A LovellW R Markesbery
May 20, 1998·Journal of the Neurological Sciences·Y AndoM Ando
Dec 5, 1998·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·D PraticòG A Fitzgerald
Dec 11, 1999·Archives of Neurology·W R Markesbery
Nov 7, 2000·The American Journal of Medicine·D Praticò, N Delanty
Jun 5, 2002·Current Opinion in Lipidology·Sönke ArltAnatol Kontush
Sep 5, 2002·Free Radical Biology & Medicine·Thomas J MontineJason D Morrow
Apr 3, 2003·Neuron·Flavio KamenetzRoberto Malinow
Apr 12, 2003·Progress in Lipid Research·Koji Uchida
Jun 25, 2003·The Journal of Biological Chemistry·Vishwanath KoppakaPaul H Axelsen
Aug 2, 2003·Molecular Aspects of Medicine·Yogesh C AwasthiSanjay Awasthi
Aug 2, 2003·Molecular Aspects of Medicine·Quan LiuGeorge Perry
May 5, 2004·Archives of General Psychiatry·Ara S KhachaturianUNKNOWN Cache County Study Investigators
Oct 14, 2004·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·Jaime E RofinaErik Gruys
May 26, 2005·Brain Pathology·Olivier BoutaudJohn A Oates
Jul 5, 2005·Journal of Neurochemistry·Irene Zagol-IkapitteJohn A Oates
Sep 15, 2005·Biochemistry·Ian V J MurrayPaul H Axelsen
Dec 23, 2006·Proceedings of the National Academy of Sciences of the United States of America·Jonathan T TingJane M Sullivan

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Citations

Jan 12, 2019·British Journal of Pharmacology·Sara NiksereshtScott Ayton
Jun 9, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Bruce A BerkowitzRobin Roberts
Oct 24, 2018·Cell Communication and Signaling : CCS·Julianna KardosKatalin Jemnitz
Jan 11, 2020·Frontiers in Neuroscience·Victor Tapias
Mar 7, 2021·Chemistry and Physics of Lipids·Sara García-ViñualesDanilo Milardi
Nov 15, 2020·Ageing Research Reviews·Scott Ayton, Ashley I Bush

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