Toxic effect of a β-amyloid peptide (β22–35) on the hippocampal neuron and its prevention

Takadera, Tsuneo; Sakura, Naoki; Mohri, Tetsuro; Hashimoto, Tadashi

doi:10.1016/0304-3940(93)90135-8

Cited by 77 publications

(52 citation statements)

References 20 publications

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“…To determine whether MitoQ can prevent A β toxicity in primary neurons and to explore its effect on mitochondria, we investigated its effects on mouse cortical neurons treated with A β (22–35) in cell culture. This A β peptide fragment contains the biologically active portion of A β (Yanker et al, 1990; Takadera et al, 1993). It has the experimental advantage for in vitro studies of rapidly aggregating in aqueous solutions (Pike et al, 1993).…”

Section: Resultsmentioning

confidence: 99%

The Mitochondria-Targeted Antioxidant MitoQ Prevents Loss of Spatial Memory Retention and Early Neuropathology in a Transgenic Mouse Model of Alzheimer's Disease

McManus

Murphy²,

Franklin³

2011

J. Neurosci.

366

222

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Considerable evidence suggests that mitochondrial dysfunction and oxidative stress contribute to the progression of Alzheimer’s disease (AD). We examined the ability of the novel mitochondria-targeted antioxidant MitoQ (mitoquinone mesylate: [10-(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cycloheexadienlyl) decyl triphenylphosphonium methanesulfonate]) to prevent AD-like pathology in mouse cortical neurons in cell culture and in a triple transgenic mouse model of AD (3xTg-AD). MitoQ attenuated β-amyloid (Aβ)-induced neurotoxicity in cortical neurons and also prevented increased production of reactive species and loss of mitochondrial membrane potential (Δψm) in them. To determine whether the mitochondrial protection conferred by MitoQ was sufficient to prevent the emergence of AD-like neuropathology in vivo, we treated young female 3xTg-AD mice with MitoQ for 5 months and analyzed the effect on the progression of AD-like pathologies. Our results show that MitoQ prevented cognitive decline in these mice as well as oxidative stress, Aβ accumulation, astrogliosis, synaptic loss, and caspase activation in their brains. The work presented herein suggests a central role for mitochondria in neurodegeneration and provides evidence supporting the use of mitochondria-targeted therapeutics in diseases involving oxidative stress and metabolic failure, namely AD.

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Section: Resultsmentioning

confidence: 99%

The Mitochondria-Targeted Antioxidant MitoQ Prevents Loss of Spatial Memory Retention and Early Neuropathology in a Transgenic Mouse Model of Alzheimer's Disease

McManus

Murphy²,

Franklin³

2011

J. Neurosci.

366

222

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“…Moreover, insulin is capable of reducing the Aβ-induced impairment of LTP through the prevention of Aβ oligomerization [175]. Reduction of Aβ22-35 neurotoxicity by insulin is also reported on the cultured rat hippocampal neurons [288].…”

Section: Protective Effects Against Beta Amyloid Toxicitymentioning

confidence: 96%

Insulin in the Brain: Sources, Localization and Functions

et al. 2012

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Historically, insulin is best known for its role in peripheral glucose homeostasis, and insulin signaling in the brain has received less attention. Insulin-independent brain glucose uptake has been the main reason for considering the brain as an insulin-insensitive organ. However, recent findings showing a high concentration of insulin in brain extracts, and expression of insulin receptors (IRs) in central nervous system tissues have gathered considerable attention over the sources, localization, and functions of insulin in the brain. This review summarizes the current status of knowledge of the peripheral and central sources of insulin in the brain, site-specific expression of IRs, and also neurophysiological functions of insulin including the regulation of food intake, weight control, reproduction, and cognition and memory formation. This review also considers the neuromodulatory and neurotrophic effects of insulin, resulting in proliferation, differentiation, and neurite outgrowth, introducing insulin as an attractive tool for neuroprotection against apoptosis, oxidative stress, beta amyloid toxicity, and brain ischemia.

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“…Among such roles, brain insulin has been proposed to increase neurite outgrowth [136, 137] and regeneration of small myelinated fibers [2, 138], maintain cortical, sympathetic and sensory neuronal survival during nervous system development [139, 140], stimulate neuronal protein synthesis [2], and improve synaptic activity and plasticity, memory formation, and storage [110], as well as neuroprotection [141–143]. In this regard, insulin administration has been shown to improve memory/learning in rats [39] and in healthy humans (after intranasal administration), without changes in peripheral glycemia [12, 144].…”

Section: Role Of Insulin and Igf-1 In The Brainmentioning

confidence: 99%

Insulin in Central Nervous System: More than Just a Peripheral Hormone

Duarte

Moreira

Oliveira

2012

Journal of Aging Research

250

202

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Insulin signaling in central nervous system (CNS) has emerged as a novel field of research since decreased brain insulin levels and/or signaling were associated to impaired learning, memory, and age-related neurodegenerative diseases. Thus, besides its well-known role in longevity, insulin may constitute a promising therapy against diabetes- and age-related neurodegenerative disorders. More interestingly, insulin has been also faced as the potential missing link between diabetes and aging in CNS, with Alzheimer's disease (AD) considered as the “brain-type diabetes.” In fact, brain insulin has been shown to regulate both peripheral and central glucose metabolism, neurotransmission, learning, and memory and to be neuroprotective. And a future challenge will be to unravel the complex interactions between aging and diabetes, which, we believe, will allow the development of efficient preventive and therapeutic strategies to overcome age-related diseases and to prolong human “healthy” longevity. Herewith, we aim to integrate the metabolic, neuromodulatory, and neuroprotective roles of insulin in two age-related pathologies: diabetes and AD, both in terms of intracellular signaling and potential therapeutic approach.

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Toxic effect of a β-amyloid peptide (β22–35) on the hippocampal neuron and its prevention

Cited by 77 publications

References 20 publications

The Mitochondria-Targeted Antioxidant MitoQ Prevents Loss of Spatial Memory Retention and Early Neuropathology in a Transgenic Mouse Model of Alzheimer's Disease

The Mitochondria-Targeted Antioxidant MitoQ Prevents Loss of Spatial Memory Retention and Early Neuropathology in a Transgenic Mouse Model of Alzheimer's Disease

Insulin in the Brain: Sources, Localization and Functions

Insulin in Central Nervous System: More than Just a Peripheral Hormone

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