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Interactions with and Membrane Permeabilization of Brain Mitochondria by Amyloid Fibrils
Published on: September 28, 2019
Abeta and human amylin share a common toxicity pathway via mitochondrial dysfunction
Yun-An Lim1, Virginie Rhein, Ginette Baysang
1Alzheimer's & Parkinson's Disease Laboratory, Brain & Mind Research Institute, University of Sydney, Camperdown, Australia.
Proteomics
|February 27, 2010
Summary
Alzheimer's disease and type 2 diabetes share common molecular pathways, particularly mitochondrial dysfunction, driven by amyloid beta and human amylin. Targeting these shared mechanisms may offer therapeutic benefits for both conditions.
Area of Science:
- Biochemistry
- Neuroscience
- Endocrinology
Background:
- Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are prevalent elderly diseases.
- Both are characterized by amyloid protein aggregation: amyloid beta (A beta) in AD and amylin in T2DM.
- Amyloid deposition leads to cellular dysfunction and loss in target tissues.
Purpose of the Study:
- To investigate shared molecular mechanisms between AD and T2DM.
- To identify common protein targets deregulated by A beta and human amylin (HA).
- To explore the role of mitochondrial dysfunction in the pathogenesis of both diseases.
Main Methods:
- Quantitative iTRAQ proteomics was employed for protein deregulation discovery.
- Functional assays assessed mitochondrial complex activities and respiration.
- Reactive oxygen species (ROS) generation was measured after peptide treatments.
Main Results:
- A beta and HA deregulated identical protein sets, with 25% being mitochondrial.
- Both HA and A beta significantly reduced mitochondrial complex IV activity and respiration.
- A beta and HA increased ROS generation, indicating oxidative stress.
Conclusions:
- Mitochondrial dysfunction is a common pathogenic mechanism in Alzheimer's disease and type 2 diabetes.
- A beta and HA exert toxicity, at least partly, through mitochondrial impairment.
- Restoring mitochondrial function may represent a therapeutic strategy for both AD and T2DM.
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