Oxidative Stress, Synaptic Dysfunction, and Alzheimer’s Disease

Journal of Alzheimer s Disease, Journal Year: 2017, Volume and Issue: 57(4), P. 1105 - 1121

Published: Jan. 6, 2017

Alzheimer's disease (AD) is a devastating neurodegenerative disorder without cure. Most AD cases are sporadic where age represents the greatest risk factor. Lack of understanding mechanism hinders development efficacious therapeutic approaches. The loss synapses in affected brain regions correlates best with cognitive impairment patients and has been considered as early that precedes neuronal loss. Oxidative stress recognized contributing factor aging progression multiple diseases including AD. Increased production reactive oxygen species (ROS) associated age- disease-dependent mitochondrial function, altered metal homeostasis, reduced antioxidant defense directly affect synaptic activity neurotransmission neurons leading to dysfunction. In addition, molecular targets by ROS include nuclear DNA, lipids, proteins, calcium dynamics cellular architecture, receptor trafficking endocytosis, energy homeostasis. Abnormal metabolism turn could accumulation amyloid-β (Aβ) hyperphosphorylated Tau protein, which independently exacerbate dysfunction production, thereby vicious cycle. While mounting evidence implicates etiology, clinical trials therapies have not produced consistent results. this review, we will discuss role oxidative AD, innovative strategies evolved based on better complexity mechanisms dual play health disease.

Language: Английский

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Mitochondrial dysfunction and oxidative stress in metabolic disorders — A step towards mitochondria based therapeutic strategies

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2016, Volume and Issue: 1863(5), P. 1066 - 1077

Published: Nov. 9, 2016

Language: Английский

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Oxidative stress and mitochondrial dysfunction in Alzheimer's disease

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2013, Volume and Issue: 1842(8), P. 1240 - 1247

Published: Nov. 1, 2013

Language: Английский

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Mitochondria dysfunction in the pathogenesis of Alzheimer’s disease: recent advances

Molecular Neurodegeneration, Journal Year: 2020, Volume and Issue: 15(1)

Published: May 29, 2020

Abstract Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative diseases, characterized by impaired cognitive function due to progressive loss neurons in brain. Under microscope, neuronal accumulation abnormal tau proteins and amyloid plaques are two pathological hallmarks affected brain regions. Although detailed mechanism pathogenesis AD still elusive, a large body evidence suggests that damaged mitochondria likely play fundamental roles AD. It believed healthy pool not only supports activity providing enough energy supply other related mitochondrial functions neurons, but also guards minimizing oxidative damage. In this regard, exploration multitude mechanisms altered constitutes novel promising therapeutic targets for disease. review, we will summarize recent progress underscores essential role dysfunction discuss underlying with focus on structural functional integrity including biogenesis dynamics, axonal transport, ER-mitochondria interaction, mitophagy proteostasis.

Language: Английский

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Mitochondrial defects and oxidative stress in Alzheimer disease and Parkinson disease

Free Radical Biology and Medicine, Journal Year: 2012, Volume and Issue: 62, P. 90 - 101

Published: Nov. 29, 2012

Language: Английский

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Three dimensions of the amyloid hypothesis: time, space and 'wingmen'

Nature Neuroscience, Journal Year: 2015, Volume and Issue: 18(6), P. 800 - 806

Published: May 26, 2015

Language: Английский

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Disturbed mitochondrial dynamics and neurodegenerative disorders

Nature Reviews Neurology, Journal Year: 2014, Volume and Issue: 11(1), P. 11 - 24

Published: Dec. 9, 2014

Language: Английский

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Is Alzheimer's disease a Type 3 Diabetes? A critical appraisal

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2016, Volume and Issue: 1863(5), P. 1078 - 1089

Published: Aug. 30, 2016

Language: Английский

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Impaired mitochondrial biogenesis contributes to mitochondrial dysfunction in Alzheimer’s disease

Journal of Neurochemistry, Journal Year: 2011, Volume and Issue: 120(3), P. 419 - 429

Published: Nov. 12, 2011

J. Neurochem. (2012) 120 , 419–429. Abstract Mitochondrial dysfunction is a prominent feature of Alzheimer’s disease (AD) brain. Our prior studies demonstrated reduced mitochondrial number in susceptible hippocampal neurons the brain from AD patients and M17 cells over‐expressing familial AD‐causing amyloid precursor protein (APP) mutant (APPswe). In current study, we investigated whether alterations biogenesis contribute to abnormalities AD. regulated by peroxisome proliferator activator receptor gamma‐coactivator 1α (PGC‐1α)‐nuclear respiratory factor (NRF)‐mitochondrial transcription A pathway. Expression levels PGC‐1α, NRF 1, 2, were significantly decreased both tissues APPswe cells, suggesting biogenesis. Indeed, DNA/nuclear DNA ratio, correlated with ATP content, cytochrome C oxidase activity. Importantly, over‐expression PGC‐1α could completely rescue while knockdown exacerbate impaired deficits likely involved APPswe‐induced deficits. We further that expression p‐CREB be rescued cAMP dose‐dependent manner, which inhibited PKA inhibitor H89, PKA/CREB pathway plays critical role regulation cells. Overall, this study contributes

Language: Английский

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Amyloid-Beta and Phosphorylated Tau Accumulations Cause Abnormalities at Synapses of Alzheimer’s disease Neurons

Journal of Alzheimer s Disease, Journal Year: 2016, Volume and Issue: 57(4), P. 975 - 999

Published: Aug. 27, 2016

Amyloid-beta (Aβ) and hyperphosphorylated tau are hallmark lesions of Alzheimer's disease (AD). However, the loss synapses dysfunctions neurotransmission more directly tied to severity. The role these in pathoetiological progression remains contested. Biochemical, cellular, molecular, pathological studies provided several lines evidence improved our understanding how Aβ accumulation may harm alter neurotransmission. In vitro suggests that have both direct indirect cytotoxic effects affect neurotransmission, axonal transport, signaling cascades, organelle function, immune response ways lead synaptic neurotransmitter release. Observations preclinical models autopsy support findings, suggesting while pathoetiology positive elusive, their removal reduce severity progression. purpose this article is highlight need for further investigation its interactions with neurotransmitters alike.

Language: Английский

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