Alzheimer's Disease: Recent Concepts on the Relation of Mitochondrial Disturbances, Excitotoxicity, Neuroinflammation, and Kynurenines

Journal of Alzheimer's Disease : JAD
Dénes ZádoriLászló Vécsei

Abstract

The pathomechanism of Alzheimer's disease (AD) certainly involves mitochondrial disturbances, glutamate excitotoxicity, and neuroinflammation. The three main aspects of mitochondrial dysfunction in AD, i.e., the defects in dynamics, altered bioenergetics, and the deficient transport, act synergistically. In addition, glutamatergic neurotransmission is affected in several ways. The balance between synaptic and extrasynaptic glutamatergic transmission is shifted toward the extrasynaptic site contributing to glutamate excitotoxicity, a phenomenon augmented by increased glutamate release and decreased glutamate uptake. Neuroinflammation in AD is predominantly linked to central players of the innate immune system, with central nervous system (CNS)-resident microglia, astroglia, and perivascular macrophages having been implicated at the cellular level. Several abnormalities have been described regarding the activation of certain steps of the kynurenine (KYN) pathway of tryptophan metabolism in AD. First of all, the activation of indolamine 2,3-dioxygenase, the first and rate-limiting step of the pathway, is well-demonstrated. 3-Hydroxy-L-KYN and its metabolite, 3-hydroxy-anthranilic acid have pro-oxidant, antioxidant, and potent immu...Continue Reading

References

Mar 1, 1992·Journal of the Neurological Sciences·M F BealE D Bird
Dec 1, 1992·Journal of Neuroscience Research·L S PerlmutterH C Chui
Oct 1, 1991·Neurochemical Research·C Rios, A Santamaria
Apr 1, 1990·Neurology·T I Mandybur, C C Chuirazzi
Nov 1, 1990·Neurochemical Research·C L Eastman, T R Guilarte
Aug 1, 1990·Neurology·W D ParkerJ K Parks
Oct 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·W S GriffinC Araoz
Jan 1, 1989·European Archives of Psychiatry and Neurological Sciences·E SoficK Jellinger
Oct 23, 1989·Neuroscience Letters·M M MourdianM M Mouradian
Apr 1, 1988·British Journal of Pharmacology·J H Connick, T W Stone
Jul 10, 1981·European Journal of Pharmacology·T W Stone, M N Perkins
Dec 1, 1994·Journal of Neurochemistry·E M MutisyaM F Beal
Nov 1, 1994·Annals of Neurology·P MecocciM F Beal
Dec 1, 1993·Journal of Neurochemistry·F MastrogiacomoS J Kish
Feb 1, 1993·Biochemical Society Transactions·M P Heyes
Dec 1, 1996·The Biochemical Journal·M P HeyesS P Markey
Feb 1, 1997·Neurochemistry International·S StípekT Zima
Jan 20, 1997·Neuroreport·M G EspeyC A Colton
Aug 1, 1997·Journal of Neuropathology and Experimental Neurology·S LiE Masliah
May 5, 1999·Journal of Neural Transmission·H BaranL Deecke
Oct 26, 1999·Neurology·T J MontineJ D Morrow
Mar 10, 2000·Brain Research·E Rodríguez-MartínezA Santamaría

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Citations

Jun 6, 2019·Expert Opinion on Drug Discovery·Juan F GonzálezJose María Sánchez-Montero
Apr 12, 2020·Biomolecules·Marta González-SánchezEva Carro
Jun 13, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Nana MaJun Wan
Oct 18, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ferenc ZádorLászló Vécsei
Sep 12, 2019·Frontiers in Pharmacology·Knut BiberThomas Möller
Jun 9, 2018·Nutrients·Anna E KirklandKathleen F Holton
Aug 23, 2019·Physiological Reviews·David S Wishart
May 13, 2020·International Journal of Molecular Sciences·Cristina AngeloniTullia Maraldi
May 22, 2019·International Journal of Molecular Sciences·Maria Ceprian, Daniel Fulton
Aug 10, 2019·Frontiers in Pharmacology·Sarah BeggiatoLuca Ferraro
Nov 30, 2019·Alzheimer's Research & Therapy·Vera van der VelpenJulius Popp
Jul 18, 2020·Journal of Alzheimer's Disease : JAD·Kristen R HollingerBarbara S Slusher
Apr 25, 2019·Neurotoxicity Research·Marcos Roberto de OliveiraClaudia Marlise Balbinotti Andrade
Oct 31, 2020·Clinical Psychopharmacology and Neuroscience : the Official Scientific Journal of the Korean College of Neuropsychopharmacology·Ather Muneer
Jan 12, 2021·Current Medical Science·Chuan-Cong ZhuXiao-Chuan Wang
Oct 28, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Takuya FujiwaraMakoto Tsunoda
Nov 24, 2020·Frontiers in Endocrinology·Jorge Berlanga-AcostaPedro A Valdés-Sosa
Apr 9, 2021·Pharmacology & Therapeutics·Marta Marszalek-GrabskaWaldemar A Turski
May 4, 2020·Progress in Neurobiology·Michel MaitreAyikoe-Guy Mensah-Nyagan
Jul 3, 2021·Nutrients·Gustavo Ignacio Vazquez-CervantesBenjamín Pineda
Sep 4, 2020·Journal of Neurochemistry·Marah C RuntschStefano Angiari
Jul 28, 2021·The International Journal on Drug Policy·Michael VoronkovStephen E Lankenau
Aug 10, 2021·Journal of Alzheimer's Disease : JAD·Mariana Van ZellerCláudia A Valente
Feb 20, 2020·Molecular Therapy. Nucleic Acids·Ana Teresa Barros-ViegasAna Luísa Cardoso

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