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 November 2005

Substitution of methionine 35 inhibits apoptotic effects of Abeta(31-35) and Abeta(25-35) fragments of amyloid-beta protein in PC12 cells.

Maria Elisabetta Clementi, Francesco Misiti

Med Sci Monit 2005; 11(11): BR381-385 :: ID: 430276

Abstract

BACKGROUND: Amyloid-beta peptide (AbetaP), the central constituent of senile plaques in Alzheimer's disease (AD) brain, has been shown to be toxic to neuronal cells and that this toxicity is responsible for the progressive cognitive decline associated with this neurodegenerative disease. The precise mechanism of AbetaP action remains to be determined; however, it has been reported that the methionine residue at position 35 plays a pivotal role in the toxicity of the peptide. With this in mind, the present study examines the effect of mutating the methionine to norleucine in the fragments (31-35) and (25-35) of AbetaP, which have methionine at the C-terminal, in order to investigate the influence of this residue on Abeta-mediated toxic effects on PC12 cells. MATERIAL/METHODS: The toxic and apoptotic effects (release of Cyt c, caspase activation, and DNA fragmentation) exerted by the Abeta(31-35) and Abeta(25-35) wild-type peptides and Abeta(31-35)Met-->Nle, Abeta(25-35)Met-->Nle peptides where methionine was substituted with norleucine were investigated on PC12 cells. RESULTS: The results obtained shown that both peptides induce neurotoxicity in PC12 cells via an apoptotic cell death pathway, including cytochrome c release, caspase activation, and DNA fragmentation. Furthermore, this study reveals that these events were completely abrogated in cells exposed to Abeta peptides in which methionine 35 was substituted by a norleucine residue. CONCLUSIONS: On the basis of the results obtained in this study, an additional hypothesis involving the amyloid-beta peptide and the role of Met-35 has been proposed to clarify the mechanisms responsible of neurodegeneration in Alzheimer's disease.

Keywords: Amino Acid Substitution - genetics, Amyloid beta-Peptides - toxicity, Caspases - analysis, Cytochromes c - analysis, Methionine - genetics, Neurons - enzymology, Norleucine - genetics, Peptide Fragments - toxicity

Add Comment 0 Comments

Editorial

01 February 2025 : Editorial  

Editorial: Current Approaches to Screening for Lung Cancer in Smokers and Non-Smokers

Dinah V. Parums

DOI: 10.12659/MSM.948255

Med Sci Monit 2025; 31:e948255

0:00

In Press

Clinical Research  

Correlation Descriptive Study on Nurses' Professional Values and Job Satisfaction and the Ethical Climate o...

Med Sci Monit In Press; DOI: 10.12659/MSM.945639  

Clinical Research  

Pre- and Post-Surgical MRI Analysis of Levator Ani in Pelvic Organ Prolapse Patients: A Single-Center Study

Med Sci Monit In Press; DOI: 10.12659/MSM.945993  

Clinical Research  

Comparative Impact of Kinesio Taping and Post-Isometric Muscle Relaxation on Pain and Myofascial Mechanics ...

Med Sci Monit In Press; DOI: 10.12659/MSM.945376  

Clinical Research  

Surgical Efficacy in Varicocele Ligation with Ephedrine-Assisted Blood Pressure Control

Med Sci Monit In Press; DOI: 10.12659/MSM.946234  

Most Viewed Current Articles

17 Jan 2024 : Review article   6,968,210

Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron Variant

DOI :10.12659/MSM.942799

Med Sci Monit 2024; 30:e942799

0:00

16 May 2023 : Clinical Research   701,772

Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...

DOI :10.12659/MSM.940387

Med Sci Monit 2023; 29:e940387

0:00

01 Mar 2024 : Editorial   25,357

Editorial: First Regulatory Approvals for CRISPR-Cas9 Therapeutic Gene Editing for Sickle Cell Disease and ...

DOI :10.12659/MSM.944204

Med Sci Monit 2024; 30:e944204

0:00

28 Jan 2024 : Review article   19,972

A Review of IgA Vasculitis (Henoch-Schönlein Purpura) Past, Present, and Future

DOI :10.12659/MSM.943912

Med Sci Monit 2024; 30:e943912

0:00

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