Related Experiment Video

Updated: Sep 20, 2026

Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
00:15

Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils

Published on: September 28, 2019

Neurotoxic, redox-competent Alzheimer's beta-amyloid is released from lipid membrane by methionine oxidation

Kevin J Barnham1, Giuseppe D Ciccotosto, Anna K Tickler

  • 1Department of Pathology, The University of Melbourne and The Mental Health Research Institute of Victoria, Victoria 3010, Australia. kbarnham@unimelb.edu.au

The Journal of Biological Chemistry
|August 20, 2003
PubMed

Insights

Oxidized amyloid beta (Abeta) peptides are toxic to neurons and implicated in Alzheimer's disease. This toxicity involves metal coordination and hydrogen peroxide production, similar to reduced Abeta.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Pathology

Background:

  • Amyloid beta (Abeta) peptide neurotoxicity is central to Alzheimer's disease pathogenesis.
  • The precise mechanisms underlying Abeta-induced neuronal toxicity remain debated.
  • Oxidative stress and metal ion interactions are implicated in Alzheimer's disease.

Purpose of the Study:

  • To investigate the neurotoxicity of oxidized Abeta peptide (Met(O)Abeta).
  • To elucidate the mechanism of Met(O)Abeta toxicity and its relationship to reduced Abeta.
  • To determine if Met(O)Abeta contributes to elevated soluble Abeta in Alzheimer's disease.

Main Methods:

  • Synthesized and characterized Met(O)Abeta peptide.
  • Assessed neuronal cell toxicity of Met(O)Abeta.
  • Investigated the effects of clioquinol and catalase on Met(O)Abeta toxicity.
  • Examined Met(O)Abeta's interaction with Cu2+ and H2O2 production.
  • Evaluated Met(O)Abeta's ability to form ion channels and beta-sheet structures.

Main Results:

  • Met(O)Abeta exhibits toxicity to neuronal cells.
  • This toxicity is reduced by clioquinol and rescued by catalase, indicating a shared mechanism with reduced Abeta.
  • Met(O)Abeta cannot form ion channels or beta-sheet structures, challenging existing toxicity theories.
  • Met(O)Abeta coordinates Cu2+, reduces its oxidation state, and produces H2O2.

Conclusions:

  • Met(O)Abeta contributes to neuronal toxicity through mechanisms involving metal coordination and H2O2 generation.
  • The inability of Met(O)Abeta to form ion channels or beta-sheets suggests alternative pathways for Abeta-induced neurotoxicity.
  • Met(O)Abeta may play a role in the elevated soluble Abeta levels observed in Alzheimer's disease brains.

More Related Videos

Stereotaxic Infusion of Oligomeric Amyloid-beta into the Mouse Hippocampus08:16

Stereotaxic Infusion of Oligomeric Amyloid-beta into the Mouse Hippocampus

Published on: June 17, 2015

Quantitative Analysis of Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Stabilization in a Neural Model of Alzheimer's Disease (AD)06:41

Quantitative Analysis of Mitochondria-Associated Endoplasmic Reticulum Membrane (MAM) Stabilization in a Neural Model of Alzheimer's Disease (AD)

Published on: January 10, 2025

Related Concept Videos

Alzheimer Disease ll: Pathophysiology01:23

Alzheimer Disease ll: Pathophysiology

Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and microglia. Abnormal...
Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid Fibrils03:03

Amyloid Fibrils

Amyloid fibrils are aggregates of misfolded proteins.  Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils. 
Amyloid deposits were observed as early as 1639 in the liver and the spleen.   In 1854, Rudolph Virchow performed iodine staining, normally used to...
Alzheimer Disease l: Introduction01:29

Alzheimer Disease l: Introduction

Alzheimer disease is a chronic, progressive, and irreversible neurodegenerative disorder and the most common cause of dementia in older adults. It leads to gradual neuronal loss, causing cognitive decline, behavioral changes, and loss of functional independence.Risk Factors and EtiologyThe disease is multifactorial. Age is the strongest risk factor, with prevalence doubling every 5 years after age 65. Genetic factors include mutations in genes such as APP, PSEN1, and PSEN2, which are associated...
Alzheimer's Disease: Overview01:26

Alzheimer's Disease: Overview

Alzheimer's Disease (AD) is a continually advancing neurodegenerative disorder, distinguished by escalating memory loss, cognitive dysfunction, and dementia. The disease unfolds in three stages: preclinical, mild cognitive impairment (MCI), and dementia. Its onset is insidious, and the progression gradual, with the cause not well explained by other disorders.
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ and tau...
Dementia l: Introduction01:22

Dementia l: Introduction

Dementia is an acquired, progressive syndrome characterized by a decline in multiple cognitive domains severe enough to impair daily functioning and reduce independence. Although memory loss is a central feature, the diagnosis requires additional deficits involving language, executive function, visuospatial skills, judgment, calculation, or abstract reasoning. These cognitive impairments reflect underlying neurodegenerative or vascular processes that gradually disrupt neuronal networks...