GABAergic deafferentation hypothesis of brain aging and Alzheimer's disease revisited

Brain Research Bulletin
T J Marczynski

Abstract

Considering the mechanisms responsible for age- and Alzheimer's disease (AD)-related neuronal degeneration, little attention was paid to the opposing relationships between the energy-rich phosphates, mainly the availability of the adenosine triphosphate (ATP), and the activity of the glutamic acid decarboxylase (GAD), the rate-limiting enzyme synthesizing the gamma-amino butyric acid (GABA). Here, it is postulated that in all neuronal phenotypes the declining ATP-mediated negative control of GABA synthesis gradually declines and results in age- and AD-related increases of GABA synthesis. The Ca2+-independent carrier-mediated GABA release interferes with Ca2+-dependent exocytotic release of all transmitter-modulators, because the interstitial (ambient) GABA acts on axonal preterminal and terminal varicosities endowed with depolarizing GABA(A)-benzodiazepine receptors; this makes GABA the "executor" of virtually all age- and AD-related neurodegenerative processes. Such a role of GABA is diametrically opposite to that in the perinatal phase, when the carrier-mediated GABA release, acting on GABA(A)/chloride ionophore receptors, positively controls chemotactic migration of neuronal precursor cells, has trophic actions and initiates...Continue Reading

References

May 15, 1978·European Journal of Pharmacology·D W Gallager
May 1, 1977·Journal of Gerontology·G L ColemanA M Jonas
Aug 1, 1979·Annals of Neurology·I Osorio, R A Davidoff
May 19, 1978·Brain Research·C Braestrup, M Nielsen
Jan 1, 1978·Annual Review of Neuroscience·R Y Moore, F E Bloom
Mar 24, 1977·Nature·A NieoullonJ Glowinski
Jul 1, 1992·Journal of Neuroscience Research·K ChandrasekaranS I Rapoport
Jun 1, 1992·Brain Research. Molecular Brain Research·M C Mhatre, M K Ticku
Aug 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·R MorfinE E Baulieu
Apr 13, 1992·Neuroscience Letters·K MizoguchiT Tabira
Oct 1, 1992·Trends in Biochemical Sciences·J R Hepler, A G Gilman
Jul 1, 1992·Scientific American·M E Linder, A G Gilman
Jan 1, 1992·Neurology·J J Halperin, M P Heyes
Mar 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·J F FloodE Roberts
Apr 30, 1992·Biochemical and Biophysical Research Communications·H OkazakiS Ishibashi
Mar 1, 1991·Trends in Pharmacological Sciences·N J LeidenheimerR A Harris
Jul 1, 1991·Trends in Pharmacological Sciences·I Izquierdo, J H Medina
Jan 19, 1991·Lancet·I SavicS Stone-Elander
Dec 1, 1991·Trends in Neurosciences·E CherubiniY Ben-Ari
Jan 1, 1992·Journal of Neurochemistry·E E Kaufman, B F Driscoll
Jan 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·J I LuebkeP B Reiner
Aug 1, 1991·Brain Research Bulletin·S D O'ConnorM Radulovacki

❮ Previous
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Citations

Feb 16, 2000·Biochemical and Biophysical Research Communications·K M DavisJ Y Wu
Aug 22, 2013·Amino Acids·Abdeslem El IdrissiWilliam J L'amoreaux
Nov 13, 2003·Progress in Neurobiology·Willy MayoNora Abrous
Nov 11, 1999·European Journal of Pharmacology·A ItohT Nabeshima
Feb 28, 2001·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·M VirgiliA Contestabile
Jun 28, 2003·CNS Drugs·D Allan Butterfield, Chava B Pocernich
Apr 3, 2009·Journal of Neurosurgery. Pediatrics·Pawel G OchalskiP David Adelson
Mar 25, 2011·Future Medicinal Chemistry·Agenor LimonRicardo Miledi
Oct 21, 2004·Neurological Research·Xu Lin, Zhang Jun-Tian
Jun 7, 2008·Fitoterapia·D Raj, M Luczkiewicz
Mar 18, 2008·Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia·Merih IsFerda Ozkan
Apr 1, 2008·Neuroscience Letters·Abdeslem El Idrissi
Jan 29, 2008·Aging Cell·Elodie Drapeau, Djoher Nora Abrous
Aug 24, 2007·Journal of Neurochemistry·Robert A RissmanDavid M Armstrong
Mar 11, 2011·Journal of Neurochemistry·Robert A Rissman, William C Mobley
Apr 1, 2006·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Allen D Roses, Ann M Saunders
Apr 12, 2016·Frontiers in Pharmacology·Lieven D DeclercqGuy Bormans
Apr 7, 2005·Neuroscience Research·Maria T CastañedaLuis V Colom
May 28, 2014·Journal of Magnetic Resonance Imaging : JMRI·Xue BaiPeter B Barker
Jan 29, 2011·Neurobiology of Aging·Elseline HoekzemaJuan D Gispert
Mar 25, 2014·Brain Structure & Function·Monika Liguz-LecznarMalgorzata Kossut
Aug 22, 2017·International Journal of Molecular Sciences·Karan GovindpaniAndrea Kwakowsky
Feb 1, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hsiao-Chien TingHorng-Jyh Harn
Mar 25, 2005·Physiological Reviews·Djoher Nora AbrousMichel Le Moal
May 10, 2020·International Journal of Molecular Sciences·Chitra VinnakotaAndrea Kwakowsky
Oct 16, 1999·The Journal of Clinical Endocrinology and Metabolism·A J Lerner
Jan 28, 2020·Wellcome Open Research·Angharad G DavisUNKNOWN Tuberculous Meningitis International Research Consortium
Dec 3, 2016·Psychiatry Investigation·Ji Han LeeHyun Kook Lim
Jan 24, 2020·Frontiers in Aging Neuroscience·Miren EttchetoAntonio Camins
Feb 12, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Beatriz Calvo-Flores GuzmánAndrea Kwakowsky
Feb 15, 2003·Biological Research for Nursing·Joan A Masters, Joanne S Stevenson
Nov 26, 2015·Neural Computation·Osamu HoshinoKazuo Watanabe

❮ Previous
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