Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

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

Abstract

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

0 Comments

Editorial

01 January 2022 : Editorial  

Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Patients

Dinah V. Parums
Science Editor, Medical Science Monitor, International Scientific Information, Inc., Melville, NY, USA

DOI: 10.12659/MSM.935952

Med Sci Monit 2022; 28:e935952

SARS-CoV-2/COVID-19

11 January 2022 : Clinical Research  

A Remote Questionnaire-Based Study to Compare Alcohol Use in 1030 Final-Year High School Students in Split-...

Med Sci Monit In Press; DOI: 10.12659/MSM.935567  

08 November 2021 : Database Analysis  

Virtual Screening and Molecular Docking to Study the Mechanism of Chinese Medicines in the Treatment of Cor...

Med Sci Monit In Press; DOI: 10.12659/MSM.934102  

31 December 2021 : Clinical Research  

A Prospective Observational Study of 42 Patients with COVID-19 infection and a History of Hepatitis C Virus...

Med Sci Monit 2021; 27:e935075

30 December 2021 : Clinical Research  

Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...

Med Sci Monit 2021; 27:e935379

In Press

19 Jan 2022 : Clinical Research  

A Retrospective Study to Compare the Effects of Methylprednisolone and Dexamethasone in 35 Patients with An...

Med Sci Monit In Press; DOI: 10.12659/MSM.934703  

17 Jan 2022 : Clinical Research  

Unveiling the Differences in Biological Properties of Dental Pulp Stem Cells from Normal and Inflamed Pulp:...

Med Sci Monit In Press; DOI: 10.12659/MSM.934511  

14 Jan 2022 : Database Analysis  

Identification of Key Genes Associated with Brain Metastasis from Breast Cancer: A Bioinformatics Analysis

Med Sci Monit In Press; DOI: 10.12659/MSM.935071  

13 Jan 2022 : Review article  

A Review of Current Clinical Concepts in the Pathophysiology, Etiology, Diagnosis, and Management of Hyperc...

Med Sci Monit In Press; DOI: 10.12659/MSM.935821  

Most Viewed Current Articles

30 Dec 2021 : Clinical Research  

Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...

DOI :10.12659/MSM.935379

Med Sci Monit 2021; 27:e935379

01 Nov 2020 : Review article  

Long-Term Respiratory and Neurological Sequelae of COVID-19

DOI :10.12659/MSM.928996

Med Sci Monit 2020; 26:e928996

05 Mar 2020 : Clinical Research  

The Effects of Social Support on Sleep Quality of Medical Staff Treating Patients with Coronavirus Disease ...

DOI :10.12659/MSM.923549

Med Sci Monit 2020; 26:e923549

15 Apr 2020 : Clinical Research  

Psychological Impact and Coping Strategies of Frontline Medical Staff in Hunan Between January and March 20...

DOI :10.12659/MSM.924171

Med Sci Monit 2020; 26:e924171

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750