Intracellular amyloid beta-peptide (Abeta) accumulation is considered to be a key pathogenic factor in sporadic Alzheimer's disease (AD), but the mechanisms by which it triggers neuronal dysfunction remain unclear. We hypothesized that gradual mitochondrial dysfunction could play a central role in both initiation and progression of sporadic AD. Thus, we analyzed changes in mitochondrial structure and function following direct exposure to increasing concentrations of Abeta(1-42) and Abeta(25-35) in order to look more closely at the relationships between mitochondrial membrane viscosity, ATP synthesis, ROS production, and cytochrome c release. Our results show the accumulation of monomeric Abeta within rat brain and muscle mitochondria. Subsequently, we observed four different and additive modes of action of Abeta, which were concentration dependent: (i) an increase in mitochondrial membrane viscosity with a concomitant decrease in ATP/O, (ii) respiratory chain complexes inhibition, (iii) a potentialization of ROS production, and (iv) cytochrome c release.
Titolo: | Gradual alteration of mitochondrial structure and function by β-amyloids: importance of membrane viscosity changes, energy deprivation, ROS production and cytochrome c release. |
Autore/i: | A.L.E.A.R.D.I. AM; B.E.N.A.R.D. G, A.U.G.E.R.E.A.U. O; MALGAT; TALBOT JC; M.A.Z.A.T. JP; LETELLIER T; DACHARY P.R.I.G.E.N.T. J; SOLAINI, GIANCARLO; R.O.S.S.I.G.N.O.L. R. |
Autore/i Unibo: | |
Anno: | 2005 |
Rivista: | |
Abstract: | Intracellular amyloid beta-peptide (Abeta) accumulation is considered to be a key pathogenic factor in sporadic Alzheimer's disease (AD), but the mechanisms by which it triggers neuronal dysfunction remain unclear. We hypothesized that gradual mitochondrial dysfunction could play a central role in both initiation and progression of sporadic AD. Thus, we analyzed changes in mitochondrial structure and function following direct exposure to increasing concentrations of Abeta(1-42) and Abeta(25-35) in order to look more closely at the relationships between mitochondrial membrane viscosity, ATP synthesis, ROS production, and cytochrome c release. Our results show the accumulation of monomeric Abeta within rat brain and muscle mitochondria. Subsequently, we observed four different and additive modes of action of Abeta, which were concentration dependent: (i) an increase in mitochondrial membrane viscosity with a concomitant decrease in ATP/O, (ii) respiratory chain complexes inhibition, (iii) a potentialization of ROS production, and (iv) cytochrome c release. |
Data prodotto definitivo in UGOV: | 2005-10-17 11:50:39 |
Appare nelle tipologie: | 1.01 Articolo in rivista |