scholarly journals Mitochondrial Dysfunction and Oxidative Stress in Alzheimer’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Afzal Misrani ◽  
Sidra Tabassum ◽  
Li Yang
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Morphology ◽  
Therapeutic Approaches ◽  
The Impact ◽  
And Oxidative Stress

Mitochondria play a pivotal role in bioenergetics and respiratory functions, which are essential for the numerous biochemical processes underpinning cell viability. Mitochondrial morphology changes rapidly in response to external insults and changes in metabolic status via fission and fusion processes (so-called mitochondrial dynamics) that maintain mitochondrial quality and homeostasis. Damaged mitochondria are removed by a process known as mitophagy, which involves their degradation by a specific autophagosomal pathway. Over the last few years, remarkable efforts have been made to investigate the impact on the pathogenesis of Alzheimer’s disease (AD) of various forms of mitochondrial dysfunction, such as excessive reactive oxygen species (ROS) production, mitochondrial Ca2+ dyshomeostasis, loss of ATP, and defects in mitochondrial dynamics and transport, and mitophagy. Recent research suggests that restoration of mitochondrial function by physical exercise, an antioxidant diet, or therapeutic approaches can delay the onset and slow the progression of AD. In this review, we focus on recent progress that highlights the crucial role of alterations in mitochondrial function and oxidative stress in the pathogenesis of AD, emphasizing a framework of existing and potential therapeutic approaches.

scholarly journals RALBP1 in Oxidative Stress and Mitochondrial Dysfunction in Alzheimer’s Disease

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3113
Author(s):  
Sanjay Awasthi ◽  
Ashly Hindle ◽  
Neha A. Sawant ◽  
Mathew George ◽  
Murali Vijayan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Gene Networks ◽  
Sensory Function ◽  
Expression Of Genes ◽  
The Impact

The purpose of our study is to understand the role of the RALBP1 gene in oxidative stress (OS), mitochondrial dysfunction and cognition in Alzheimer’s disease (AD) pathogenesis. The RALPB1 gene encodes the 76 kDa protein RLIP76 (Rlip). Rlip functions as a stress-responsive/protective transporter of glutathione conjugates (GS-E) and xenobiotic toxins. We hypothesized that Rlip may play an important role in maintaining cognitive function. The aim of this study is to determine whether Rlip deficiency in mice is associated with AD-like cognitive and mitochondrial dysfunction. Brain tissue obtained from cohorts of wildtype (WT) and Rlip+/− mice were analyzed for OS markers, expression of genes that regulate mitochondrial fission/fusion, and synaptic integrity. We also examined mitochondrial ultrastructure in brains obtained from these mice and further analyzed the impact of Rlip deficiency on gene networks of AD, aging, stress response, mitochondrial function, and CREB signaling. Our studies revealed a significant increase in the levels of OS markers and alterations in the expression of genes and proteins involved in mitochondrial biogenesis, dynamics and synapses in brain tissues from these mice. Furthermore, we compared the cognitive function of WT and Rlip+/− mice. Behavioral, basic motor and sensory function tests in Rlip+/− mice revealed cognitive decline, similar to AD. Gene network analysis indicated dysregulation of stress-activated gene expression, mitochondrial function and CREB signaling genes in the Rlip+/− mouse brain. Our results suggest that Rlip deficiency-associated increases in OS and mitochondrial dysfunction could contribute to the development or progression of OS-related AD processes.

scholarly journals Anxiolytic, Promnesic, Anti-Acetylcholinesterase and Antioxidant Effects of Cotinine and 6-Hydroxy-L-Nicotine in Scopolamine-Induced Zebrafish (Danio rerio) Model of Alzheimer’s Disease

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 212
Author(s):  
Razvan Stefan Boiangiu ◽  
Marius Mihasan ◽  
Dragos Lucian Gorgan ◽  
Bogdan Alexandru Stache ◽  
Lucian Hritcu
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ache Activity ◽  
Antioxidant Properties ◽  
Parent Molecule ◽  
Qpcr Analysis ◽  
The Impact ◽  
And Oxidative Stress

Cotinine (COT) and 6-hydroxy-L-nicotine (6HLN) are two nicotinic derivatives that possess cognitive-improving abilities and antioxidant properties in different rodent models of Alzheimer’s disease (AD), eluding the side-effects of nicotine (NIC), the parent molecule. In the current study, we evaluated the impact of COT and 6HLN on memory deterioration, anxiety, and oxidative stress in the scopolamine (SCOP)-induced zebrafish model of AD. For this, COT and 6HLN were acutely administered by immersion to zebrafish that were treated with SCOP before testing. The memory performances were assessed in Y-maze and object discrimination (NOR) tasks, while the anxiety-like behavior was evaluated in the novel tank diving test (NTT). The acetylcholinesterase (AChE) activity and oxidative stress were measured from brain samples. The RT-qPCR analysis was used to evaluate the npy, egr1, bdnf, and nrf2a gene expression. Our data indicated that both COT and 6HLN attenuated the SCOP-induced anxiety-like behavior and memory impairment and reduced the oxidative stress and AChE activity in the brain of zebrafish. Finally, RT-qPCR analysis indicated that COT and 6HLN increased the npy, egr1, bdnf, and nrf2a gene expression. Therefore, COT and 6HLN could be used as tools for improving AD conditions.

scholarly journals The role of mitochondria-targeted antioxidant MitoQ in neurodegenerative disease

2018 ◽  
Vol 6 (1) ◽  
Author(s):  
Linlin Zhang ◽  
Aurelio Reyes ◽  
Xiangdong Wang
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Mitochondrial Dysfunction ◽  
Neurodegenerative Disease ◽  
And Oxidative Stress

The discovery of charged molecules being able to cross the mitochondrial membrane has prompted many scholars to exploit this idea to find a way of preventing or slowing down aging. In this paper, we will focus on mitochondria-targeted antioxidants, which are cationic derivatives of plastoquinone, and in particular on the mitochondria-targeted antioxidant therapy of neurodegenerative diseases. It is well known that the accumulation of amyloid-β peptide (Aβ) in mitochondria and its related mitochondrial dysfunction are critical signatures of Alzheimer’s disease (AD). In another neurodegenerative disease, Parkinson’s disease (PD), the loss of dopaminergic neurons in the substantia nigra and the production of Lewy bodies are among their pathological features. Pathogenesis of Parkinson’s disease and Alzheimer’s disease has been frequently linked to mitochondrial dysfunction and oxidative stress. Recent studies show that MitoQ, a mitochondria-targeted antioxidant, may possess therapeutic potential for Aβ-related and oxidative stress-associated neurodegenerative diseases, especially AD. Although MitoQ has been developed to the stage of clinical trials in PD, its true clinical effect still need further verification. This review aims to discuss the role of mitochondrial pathology in neurodegenerative diseases, as well as the recent development of mitochondrial targeted antioxidants as a potential treatment for these diseases by removing excess oxygen free radicals and inhibiting lipid peroxidation in order to improve mitochondrial function.

scholarly journals Role of RALBP1 in Oxidative Stress and Mitochondrial Dysfunction in Alzheimer's Disease

2021 ◽  
Author(s):  
Sanjay Awasthi ◽  
Ashly Hindle ◽  
Neha Sawant ◽  
Mathew George ◽  
Murali Vijayan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Sensory Function ◽  
Expression Of Genes

The purpose of our study is to understand the role of the Ralbp1 gene in oxidative stress (OS), mitochondrial dysfunction and cognition in Alzheimer's disease (AD) pathogenesis. The Ralbp1 gene encodes the 76 kDa protein Rlip (aka RLIP76). Previous studies have revealed its role in OS-related cancer. However, Rlip is transcriptionally regulated by EP300, a CREB-binding protein that is important for synaptic plasticity in the brain. Rlip functions as a stress-responsive/protective transporter of glutathione conjugates (GS-E) and xenobiotic toxins. OS causes rapid cellular accumulation of Rlip and its translocation from a tubulin-bound complex to the plasma membrane, mitochondria and nucleus. Therefore, Rlip may play an important role in maintaining cognitive function in the face of OS-related injury. This study is aimed to determine whether Rlip deficiency in mice is associated with AD-like cognitive and mitochondrial dysfunction. Brain tissue obtained from cohorts of wildtype and Rlip+/- mice were analyzed for OS markers, expression of genes that regulate mitochondrial fission/fusion, and synaptic integrity. We also examined mitochondrial ultrastructure in mouse brains obtained from these mice and further analyzed the impact of Rlip deficiency on gene networks of AD, aging, inhibition of stress-activated gene expression, mitochondrial function, and CREB signaling. Our studies revealed a significant increase in the levels of OS markers and alterations in the expression of genes and proteins involved in mitochondrial biogenesis, dynamics and synapses in brain tissues of these mice. Furthermore, we compared the cognitive function of wildtype and Rlip+/- mice. Behavioral, basic motor and sensory function tests in Rlip+/- mice revealed cognitive decline, similar to AD. Gene network analysis indicated dysregulation of stress-activated gene expression, mitochondrial function, and CREB signaling genes in the Rlip+/- mouse liver. Our results suggest that the Rlip deficiency-associated increase in OS and mitochondrial dysfunction could contribute to the development of OS-related AD processes. Therefore, the restoration of Rlip activity and endogenous cytoprotective mechanisms by pharmacological interventions is a novel approach to protect against AD.

Mitochondrial Dysfunction and Oxidative Stress in Alzheimer's Disease

2010 ◽  
Vol 5 (1) ◽  
pp. 17 ◽  
Author(s):  
Paula I Moreira ◽  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mitochondrial Dysfunction ◽  
Cell Function ◽  
Apoptotic Pathway ◽  
Life And Death ◽  
Cell Life ◽  
Oxidative Species ◽  
And Oxidative Stress

Oxidative stress and mitochondrial dysfunction are important issues in understanding the pathogenesis of Alzheimer's disease (AD). Mitochondria are pivotal in controlling cell life and death not only by producing adenosine triphosphate and sequestering calcium but also by generating reactive oxidative species and serving as repositories for proteins that regulate the intrinsic apoptotic pathway. Perturbations in the physiological function of mitochondria inevitably disturb cell function, sensitise cells to neurotoxic insults and may initiate cell death, all significant phenomena in the pathogenesis of AD. This article discusses evidence supporting the notion that mitochondrial dysfunction and oxidative stress are intimately involved in AD pathophysiology.

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