Maintenance of mitochondrial homeostasis for Alzheimer's disease: Strategies and challenges

Han, Ying; Liu, Daozhou; Cheng, Ying; Q, Ji; Liu, Miao; Zhang, Bang-Le; Zhou, Siyuan

doi:10.1016/j.redox.2023.102734

Cited by 9 publications

(4 citation statements)

References 126 publications

(148 reference statements)

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“…To fully understand its potential therapeutic benefits, further studies are needed to elucidate the contribution of other important mechanisms and mediators responsible for these effects, including the involvement of neurotrophic factors, mitochondrial homeostasis and biogenesis, apoptosis, autophagy, and neurotransmitter regulation. [49][50][51]…”

Section: Discussionmentioning

confidence: 99%

Unraveling the therapeutic potential of ginsenoside compound Mc1 in Alzheimer’s disease: Exploring the role of AMPK/SIRT1/NF-κB signaling pathway and mitochondrial function

Yuan,

Yang

2024

Adv Clin Exp Med

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Background. Alzheimer's disease (AD) is a disabling neurodegenerating disorder characterized by chronic neuroinflammation, cognitive impairment and memory loss. Current treatment options for AD offer limited benefits, underscoring the urgent need for alternative therapeutics. Despite the promising effects of ginsenosides in neurodegenerative diseases, the therapeutic potential of ginsenoside compound Mc1 (GCMc1) in AD remains to be thoroughly investigated.Objectives. This study aimed to investigate the therapeutic potential of GCMc1 in rats with AD and to elucidate the molecular mechanisms responsible for its effects. Materials and methods.Alzheimer's disease was induced in Sprague Dawley rats through a single intracerebro-ventricular injection of amyloid-beta (Aβ)1-42 peptide. The animals were divided into 5 groups: a control group and 4 AD subgroups, with or without receiving 10 mg/kg of GCMc1 and/or 100 μg/kg of compound C intraperitoneally (ip.). Behavioral tests, mitochondrial function, inflammatory cytokines, and proteins expression were evaluated using the Morris water maze (MWM) test, fluorometry, enzyme-linked immunosorbent assay (ELISA), and immunoblotting techniques, respectively. Results.Treatment with GCMc1 improved cognitive function, reduced hippocampal Aβ accumulation, and suppressed interleukin (IL)-1β, IL-10 and tumor necrosis factor alpha (TNF-α) levels. Ginsenoside compound Mc1 reduced mitochondrial reactive oxygen species (ROS) levels and membrane depolarization, increased adenosine triphosphate (ATP) levels, upregulated the expression of AMPK, PGC-1α and SIRT1 proteins, and downregulated the nuclear factor-kappa-B (NF-κB) expression. Importantly, co-administration of compound C, an AMPK inhibitor, attenuated the beneficial effects of GCMc1, suggesting the involvement of AMPK pathway in mediating GCMc1's neuroprotective effects.Conclusions. We showed that GCMc1 confers substantial neuroprotection in rats with AD by modulating the AMPK/SIRT1/NF-κB signaling pathway. These findings highlight the potential of GCMc1 as a promising therapeutic agent for AD treatment.

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Section: Discussionmentioning

confidence: 99%

Unraveling the therapeutic potential of ginsenoside compound Mc1 in Alzheimer’s disease: Exploring the role of AMPK/SIRT1/NF-κB signaling pathway and mitochondrial function

Yuan,

Yang

2024

Adv Clin Exp Med

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“…There is high demand for ATP in the very metabolically active neurons in the brain and oxidative phosphorylation, occurring in the inner mitochondrial membrane, is the process in which ATP production and ROS generation are linked [31]. Oxidative phosphorylation has been shown to play a role in AD progression, likely through oxidative damage [32][33][34]. Biffi et al used the Alzheimer's Disease Neuroimaging Initiative (ADNI) database to gather SNP genotype and baseline MRI results from 740 subjects in four clinical categories (cognitively normal controls, MCI non-converters, MCI converted to AD, AD) [35].…”

Section: Atp and Oxidative Phosphorylationmentioning

confidence: 99%

Mitochondria in Alzheimer’s Disease Pathogenesis

Reiss,

Gulkarov,

Jacob

et al. 2024

Life

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Alzheimer’s disease (AD) is a progressive and incurable neurodegenerative disorder that primarily affects persons aged 65 years and above. It causes dementia with memory loss and deterioration in thinking and language skills. AD is characterized by specific pathology resulting from the accumulation in the brain of extracellular plaques of amyloid-β and intracellular tangles of phosphorylated tau. The importance of mitochondrial dysfunction in AD pathogenesis, while previously underrecognized, is now more and more appreciated. Mitochondria are an essential organelle involved in cellular bioenergetics and signaling pathways. Mitochondrial processes crucial for synaptic activity such as mitophagy, mitochondrial trafficking, mitochondrial fission, and mitochondrial fusion are dysregulated in the AD brain. Excess fission and fragmentation yield mitochondria with low energy production. Reduced glucose metabolism is also observed in the AD brain with a hypometabolic state, particularly in the temporo-parietal brain regions. This review addresses the multiple ways in which abnormal mitochondrial structure and function contribute to AD. Disruption of the electron transport chain and ATP production are particularly neurotoxic because brain cells have disproportionately high energy demands. In addition, oxidative stress, which is extremely damaging to nerve cells, rises dramatically with mitochondrial dyshomeostasis. Restoring mitochondrial health may be a viable approach to AD treatment.

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“…These mitochondrial regulations are known as mitochondrial quality control (MQC). Moreover, MQC is associated with a variety of diseases, such as aging ( Okatani et al, 2002 ; Zhang et al, 2023 ), cancers ( de Almeida Chuffa et al, 2019 ; Reiter et al, 2020a ; Zhang et al, 2023 ), cardiomyopathy ( Cai et al, 2022 ; Zhou et al, 2023 ), intestinal inflammation ( Motilva et al, 2011 ; Ma et al, 2020 ), ischemia/reperfusion injury ( Chen et al, 2016 ; Bai et al, 2023 ), liver disease ( Mauriz et al, 2007 ; Solís-Muñoz et al, 2011 ; Zhou et al, 2018a ), and neurodegenerative diseases ( Jauhari et al, 2020 ; Hossain et al, 2021 ; Austad et al, 2022 ; Xu et al, 2023 ; Han et al, 2023 ). Therefore, revealing the molecular mechanisms of MQC dysregulated may provide new prospects for therapeutic drug development in related diseases.…”

Section: Introductionmentioning

confidence: 99%

The potential influence of melatonin on mitochondrial quality control: a review

Lei,

Xu,

Huang

et al. 2024

Front. Pharmacol.

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Mitochondria are critical for cellular energetic metabolism, intracellular signaling orchestration and programmed death regulation. Therefore, mitochondrial dysfunction is associated with various pathogeneses. The maintenance of mitochondrial homeostasis and functional recovery after injury are coordinated by mitochondrial biogenesis, dynamics and autophagy, which are collectively referred to as mitochondrial quality control. There is increasing evidence that mitochondria are important targets for melatonin to exert protective effects under pathological conditions. Melatonin, an evolutionarily conserved tryptophan metabolite, can be synthesized, transported and metabolized in mitochondria. In this review, we summarize the important role of melatonin in the damaged mitochondria elimination and mitochondrial energy supply recovery by regulating mitochondrial quality control, which may provide new strategies for clinical treatment of mitochondria-related diseases.

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Maintenance of mitochondrial homeostasis for Alzheimer's disease: Strategies and challenges

Cited by 9 publications

References 126 publications

Unraveling the therapeutic potential of ginsenoside compound Mc1 in Alzheimer’s disease: Exploring the role of AMPK/SIRT1/NF-κB signaling pathway and mitochondrial function

Unraveling the therapeutic potential of ginsenoside compound Mc1 in Alzheimer’s disease: Exploring the role of AMPK/SIRT1/NF-κB signaling pathway and mitochondrial function

Mitochondria in Alzheimer’s Disease Pathogenesis

The potential influence of melatonin on mitochondrial quality control: a review

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