01 October 2005
Morphine via nitric oxide modulates beta-amyloid metabolism: a novel protective mechanism for Alzheimer's disease.Theodore Pak, Patrick Cadet, Kirk J Mantione, George B Stefano
Med Sci Monit 2005; 11(10): BR357-366 :: ID: 429256
Background: The deposition of intracellular and extracellular beta-amyloidpeptide (Abeta) in the brain is a pathologic feature of Alzheimer's disease (AD), a prevalent neurodegenerativedisorder. However, the exact role of the Abeta peptide in causing AD's symptoms is unclear. Material/Methods:CRL-2266 SH-SY5Y human neuroblastoma cells (ATCC, USA) and HTB-11 human neuroblastoma cells (ATCC, USA)were cultured. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to analyze theeffects of beta25-35, morphine, and SNAP treatments upon BACE-1 and BACE-2 mRNA expression semi-quantitativeRT-PCR. The production of NO in SH-SY5Y cells was detected using the Apollo 4000 Free Radical Analyzer(World Precision Instruments). Results: Untreated HTB-11 neuroblastoma cells constitutively express BACE-1and BACE-2 mRNA. Morphine down regulates the expression of BACE-1 and up regulates the expression ofBACE-2 in a naloxone antagonizable manner. When HTB-11 cells were treated with L-NAME, a cNOS inhibitor;the effects of morphine were blocked. SNAP (a NO donor) mimicked the effect of morphine. In SH-SY5Y cells,Abeta treated cells show a dose-dependent decrease in NO release, demonstrating that Ab is dose-dependentlyinhibiting the release of constitutive NO. Conclusions: Ab and morphine/NO each inhibit the productionof the other. This suggests that a deficiency of basal NO or endogenous morphine may trigger drasticallyreduced levels of basal NO. The outcome is chronic vasoconstriction and brain hypoperfusion and eventualneuronal death. This novel theorized mechanism for AD supports an increasingly-accepted vascular pathologicalhypothesis for the disease.
Keywords: Aspartic Acid Endopeptidases - genetics, Amyloid beta-Peptides - metabolism, Amyloid Precursor Protein Secretases, Alzheimer Disease - prevention & control, Endopeptidases - genetics, Gene Expression Regulation, Enzymologic - physiology, Morphine - pharmacology, Nitric Oxide - physiology, RNA, Messenger - genetics, Reverse Transcriptase Polymerase Chain Reaction
01 December 2022 : EditorialEditorial: The World Health Organization (WHO) Fungal Priority Pathogens List in Response to Emerging Fungal Pathogens During the COVID-19 Pandemic
Med Sci Monit 2022; 28:e939088
29 November 2022 : Clinical ResearchRetrospective Study to Identify Risk Factors for Severe Disease and Mortality Using the Modified Early Warn...
Med Sci Monit In Press; DOI: 10.12659/MSM.938647
24 November 2022 : Clinical ResearchA Prospective Questionnaire-Based Study to Evaluate Factors Affecting the Decision to Receive COVID-19 Vacc...
Med Sci Monit In Press; DOI: 10.12659/MSM.938665
01 December 2022 : EditorialEditorial: The World Health Organization (WHO) Fungal Priority Pathogens List in Response to Emerging Funga...
Med Sci Monit 2022; 28:e939088
05 Dec 2022 : Database AnalysisImpact of the De Ritis Ratio on the Prognosis of Patients with Stable Coronary Artery Disease Undergoing Pe...
Med Sci Monit In Press; DOI: 10.12659/MSM.937737
02 Dec 2022 : Clinical ResearchValue of Early Laparoscopic Exploration for Primary Infertile Patients with Patent Fallopian Tubes Complica...
Med Sci Monit In Press; DOI: 10.12659/MSM.938637
02 Dec 2022 : Clinical ResearchSingle-Center Study in Lithuania to Evaluate the Role of Transthoracic Impedance Cardiography in the Diagno...
Med Sci Monit In Press; DOI: 10.12659/MSM.938389
Most Viewed Current Articles
13 Nov 2021 : Clinical ResearchAcceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...
Med Sci Monit 2021; 27:e932788
30 Dec 2021 : Clinical ResearchRetrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...
Med Sci Monit 2021; 27:e935379
01 Nov 2020 : Review articleLong-Term Respiratory and Neurological Sequelae of COVID-19
Med Sci Monit 2020; 26:e928996