Alzheimer's disease: Effects of β-amyloid on mitochondria

Tillement, Laurent; Lecanu, Laurent; Papadopoulos, Vassilios

doi:10.1016/j.mito.2010.08.009

Cited by 127 publications

(84 citation statements)

References 79 publications

(96 reference statements)

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“…Moreover, Cuevas and colleagues (Cuevas et al, 2011) suggested that intrahippocampal injection of Aβ increases expression of the receptor for advanced glycation end products (RAGE), which leads to events such as enhanced production of pro-apoptotic factors and NO. The pathological effects of β-amyloid are associated with other events such as the following: increased synaptic transmission (Cuevas et al, 2011), imbalance between elevated levels of inflammatory cytokines and decreased levels of neurotrophic factors in the brain tissue (Ji et al, 2011), and mitochondrial dysfunction (Ren et al, 2011;Tillement et al, 2011). Together, these findings show that β-amyloid triggers a cascade of extra-and intracellular events, all of which may be involved in neuronal degeneration.…”

Section: Intrahippocampal Injection Of Aβ 1-40 Causes Neuronal Degenementioning

confidence: 98%

Genistein inhibits aggregation of exogenous amyloid-beta1–40 and alleviates astrogliosis in the hippocampus of rats

et al. 2012

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We addressed the question of whether injection of Aβ in the rat brain is associated with pathology in the hippocampus, and if genistein has any protective effect against the neuronal damage caused by Aβ 1-40 . Genistein is a plant-derived compound with a structure similar to that of the female sex hormone oestrogen and it was recently shown that pretreatment with a single dose of genistein ameliorated learning and memory deficits in an amyloid beta (Aβ) 1-40 rat model of Alzheimer's disease. Here, we report that injection of the amyloid peptide into the hippocampus of rats led to formation of Aβ 1-40 positive aggregates close to the lateral blade of the dentate gyrus (DGlb). We also observed the following in the hippocampus: extensive cell death in the DGlb (P < 0.0001), CA1 (P = 0.03), and CA3 (P = 0.002); an increased number of iNOS-expressing cells (P = 0.01) and gliosis. Genistein given to rats by gavage one hour before Key words: amyloid-beta, Alzheimer's disease, genistein, neuronal degeneration 1 1 Abbreviations: AD, Alzheimer's disease; iNOS, inducible nitric oxide synthase; nNOS, neuronal nitric oxide synthase; CA1, cornu ammonis 1; CA2, cornu ammonis 2; CA3, cornu ammonis 3; Aβ, amyloid beta; DGlb, lateral blade of dentate gyrus; DGmb, medial blade of dentate gyrus; GFAP, glial fibrillary acidic protein; CC, corpus callosum; MAP, mitogenactivated protein; NFĸB, nuclear factor kappa B; MnSOD, manganese superoxide dismutase; APP, amyloid precursor protein; CrEL, Cremophor EL

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Section: Intrahippocampal Injection Of Aβ 1-40 Causes Neuronal Degenementioning

confidence: 98%

Genistein inhibits aggregation of exogenous amyloid-beta1–40 and alleviates astrogliosis in the hippocampus of rats

et al. 2012

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“…This is particularly true for Alzheimer's disease which is characterized by the presence of extracellular senile plaques, mainly composed of amyloid‐β (Aβ) peptide and intracellular neurofibrillary tangles made up of hyperphosphorylated tau protein (Selkoe, 2004). Several studies demonstrate that the Aβ peptide accumulates progressively into mitochondria (Hansson Petersen et al., 2008; Manczak et al., 2006) where it inhibits the activities of the respiratory chain complex and thus oxidative phosphorylation ( Hernandez‐Zimbron et al., 2012; Lahmy, Long, Morin, Villard, & Maurice, 2015; Tillement, Lecanu, & Papadopoulos, 2011; Tsukada et al., 2014). The Aβ peptide can also potentially cause mPTP opening in vivo as it induces mitochondrial swelling, decreases mitochondrial membrane potential, and potentiates the effect of mPTP inducers in isolated brain mitochondria (Du et al., 2008; Moreira, Santos, Moreno, & Oliveira, 2001; Shevtzova, Kireeva, & Bachurin, 2001).…”

Section: Evidence For the Involvement Of Mptp Opening In Age‐associatmentioning

confidence: 99%

Mitochondria and aging: A role for the mitochondrial transition pore?

2018

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SummaryThe cellular mechanisms responsible for aging are poorly understood. Aging is considered as a degenerative process induced by the accumulation of cellular lesions leading progressively to organ dysfunction and death. The free radical theory of aging has long been considered the most relevant to explain the mechanisms of aging. As the mitochondrion is an important source of reactive oxygen species (ROS), this organelle is regarded as a key intracellular player in this process and a large amount of data supports the role of mitochondrial ROS production during aging. Thus, mitochondrial ROS, oxidative damage, aging, and aging‐dependent diseases are strongly connected. However, other features of mitochondrial physiology and dysfunction have been recently implicated in the development of the aging process. Here, we examine the potential role of the mitochondrial permeability transition pore (mPTP) in normal aging and in aging‐associated diseases.

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“…An important downstream consequence of A␤ pathology is mitochondrial toxicity (31). As synapses are high energy demanding sites, mitochondria play critical roles in maintaining synaptic function, and mitochondria toxicity likely contributes to synaptic loss in AD (32).…”

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confidence: 99%