Amyloid β peptide directly impairs pineal gland melatonin synthesis and melatonin receptor signaling through the ERK pathway

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Erika CeconRegina P Markus

Abstract

Melatonin is the hormone produced by the pineal gland known to regulate physiologic rhythms and to display immunomodulatory and neuroprotective properties. It has been reported that Alzheimer disease patients show impaired melatonin production and altered expression of the 2 G protein-coupled melatonin receptors (MTRs), MT₁ and MT₂, but the underlying mechanisms are not known. Here we evaluated whether this dysfunction of the melatonergic system is directly caused by amyloid β peptides (Aβ(1-40) and Aβ(1-42)). Aβ treatment of rat pineal glands elicited an inflammatory response within the gland, evidenced by the up-regulation of 52 inflammatory genes, and decreased the production of melatonin up to 75% compared to vehicle-treated glands. Blocking NF-κB activity prevented this effect. Exposure of HEK293 cells stably expressing recombinant MT₁ or MT₂ receptors to Aβ lead to a 40% reduction in [(125)I]iodomelatonin binding to MT₁. ERK1/2 activation triggered by MTRs, but not by the β₂-adrenergic receptor, was markedly impaired by Aβ in HEK293 transfected cells, as well as in primary rat endothelial cells expressing endogenous MTRs. Our data reveal the melatonergic system as a new target of Aβ, opening new perspectives to Alzheimer ...Continue Reading

References

Nov 17, 2001·European Journal of Pharmacology·C M LotufoR P Markus
Jun 12, 2002·The Journal of Biological Chemistry·Karie N DahlgrenMary Jo LaDu
Jul 12, 2002·Cell and Tissue Research·Morten Møller, Florian M M Baeres
Feb 28, 2003·The Journal of Pharmacology and Experimental Therapeutics·Regina P MarkusLivia A C Reno
May 8, 2003·The Journal of Biological Chemistry·Cyril Couturier, Ralf Jockers
Nov 5, 2003·Biochemistry·Brett A ChromyWilliam L Klein
Dec 13, 2003·The Journal of Clinical Endocrinology and Metabolism·Ying-Hui WuDick F Swaab
Aug 10, 2004·Journal of Pineal Research·Ling Qiang ZhuJian-Zhi Wang
Oct 16, 2004·Journal of Pineal Research·Zheng Feng, Jun-Tian Zhang
Dec 25, 2004·Journal of Pineal Research·Egemen SavaskanRalf Jockers
Oct 6, 2005·Neuroscience Letters·John LarsonHari Manev
Mar 27, 2007·Cellular Microbiology·Daniel E Voth, Robert A Heinzen
Dec 13, 2007·Neuroimmunomodulation·Regina P MarkusErika Cecon
May 22, 2008·British Journal of Pharmacology·R JockersP Delagrange
Dec 17, 2008·The Journal of Biological Chemistry·Said AbdAllaUrsula Quitterer
Dec 17, 2008·The Journal of Biological Chemistry·Said AbdAllaUrsula Quitterer
Oct 22, 2009·Science Signaling·Amantha Thathiah, Bart De Strooper
Mar 23, 2010·Cell·Christopher K GlassFred H Gage
Apr 20, 2010·Pharmacology & Therapeutics·Regina P MarkusZulma S Ferreira
Jun 8, 2010·The EMBO Journal·Deepak MittalMaria Rescigno
Jul 1, 2010·Journal of Pineal Research·Sanseray da Silveira Cruz-MachadoRegina Pekelmann Markus
Nov 26, 2010·PloS One·Eduardo Koji TamuraRegina Pekelmann Markus
Jan 21, 2011·Nature Reviews. Neuroscience·Amantha Thathiah, Bart De Strooper
Mar 2, 2011·Current Neuropharmacology·Daniel P CardinaliLuis I Brusco
Apr 8, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Tatsuya HoshinoTohru Mizushima
Jun 3, 2011·Synapse·Philip Seeman, Neil Seeman
Nov 15, 2011·Recent Patents on Endocrine, Metabolic & Immune Drug Discovery·Erika Cecon, Regina P Markus
Nov 24, 2011·Journal of Pineal Research·Sergio A Rosales-CorralRussel J Reiter
Feb 4, 2012·Genes & Development·Matthew S Hayden, Sankar Ghosh
Jan 1, 2011·Frontiers in Endocrinology·Claudia Emanuele Carvalho-SousaRegina P Markus

❮ Previous
Next ❯

Citations

Apr 16, 2016·Molecular Neurobiology·Romina María UrangaGabriela Alejandra Salvador
Nov 11, 2016·Oxidative Medicine and Cellular Longevity·Josiel Mileno MackRui Daniel Prediger
Jun 18, 2016·British Journal of Pharmacology·Ralf JockersDarius P Zlotos
May 12, 2017·British Journal of Pharmacology·Florence GbahouRalf Jockers
Oct 8, 2016·Molecular BioSystems·Soujanya D YelamanchiT S Keshava Prasad
Nov 7, 2017·British Journal of Pharmacology·Regina P MarkusMarina Marçola
Apr 14, 2019·British Journal of Pharmacology·Erika CeconRalf Jockers
Mar 17, 2017·Molecular Systems Biology·Kate SokolinaIgor Stagljar
Jul 30, 2019·Journal of Pineal Research·Leila Eliza Barbosa LimaPedro Augusto Carlos Magno Fernandes
Jan 7, 2016·Journal of Pineal Research·Luis Henrique Souza-TeodoroZ S Ferreira
May 2, 2018·Journal of Alzheimer's Disease : JAD·Yan ShiQing Tian
Nov 12, 2015·CNS Neuroscience & Therapeutics·Alessandro MartoranaGiacomo Koch
Nov 5, 2016·Journal of Alzheimer's Disease : JAD·Stephen BeesleyEwa A Bienkiewicz
May 20, 2017·Scientific Reports·Sanseray da Silveira Cruz-MachadoRegina P Markus
Jul 26, 2018·Cellular and Molecular Life Sciences : CMLS·Abla Benleulmi-ChaachouaRalf Jockers
May 28, 2020·Frontiers in Aging Neuroscience·Victoria M PakFannie Onen
Nov 23, 2020·Alzheimer's Research & Therapy·Jeongbin ParkKi Woong Kim
Mar 26, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Gianluigi MazzoccoliVictoria Polyakova
Dec 18, 2021·Frontiers in Endocrinology·Yan MengLin Tao

❮ Previous
Next ❯

Related Concepts

Related Feeds

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Adrenergic Receptors: Trafficking

Adrenergic receptor trafficking is an active physiological process where adrenergic receptors are relocated from one region of the cell to another or from one type of cell to another. Discover the latest research on adrenergic receptor trafficking here.