The Natural Alkaloid Palmatine Selectively Induces Mitophagy and Restores Mitochondrial Function in an Alzheimer’s Disease Mouse Model

Lee, Da-Ye; Lee, Kang-Min; Um, Jee-Hyun; Kim, Young-Yeon; Kim, Dong-Hyun; Yun, Jeanho

doi:10.3390/ijms242216542

Cited by 8 publications

(2 citation statements)

References 58 publications

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“…Target mitophagy, a specific form of autophagy that degrades mitochondria exclusively ( Lu et al, 2023 ), may also be a viable approach to alleviate myopathies associated with excessive oxidative stress ( Ito et al, 2022 ). Traditional mitophagy inducers like oligomycin and carbonyl cyanide m-chlorophenyl hydrazone (CCCP) have been widely adopted in the in vitro system but their high toxicity limits their clinical applicability ( Lee et al, 2023 ). Therefore, considerable efforts have been devoted to screen for alternative inducers with low toxicity for clinical applications.…”

Section: Targeting Mitochondrial Health As a New Treatment Strategy O...mentioning

confidence: 99%

Mitochondrial defects in sporadic inclusion body myositis—causes and consequences

Iu,

So,

Chan

2024

Front. Cell Dev. Biol.

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Sporadic inclusion body myositis (sIBM) is a distinct subcategory of Idiopathic Inflammatory Myopathies (IIM), characterized by unique pathological features such as muscle inflammation, rimmed vacuoles, and protein aggregation within the myofibers. Although hyperactivation of the immune system is widely believed as the primary cause of IIM, it is debated whether non-immune tissue dysfunction might contribute to the disease’s onset as patients with sIBM are refractory to conventional immunosuppressant treatment. Moreover, the findings that mitochondrial dysfunction can elicit non-apoptotic programmed cell death and the subsequent immune response further support this hypothesis. Notably, abnormal mitochondrial structure and activities are more prominent in the muscle of sIBM than in other types of IIM, suggesting the presence of defective mitochondria might represent an overlooked contributor to the disease onset. The large-scale mitochondrial DNA deletion, aberrant protein aggregation, and slowed organelle turnover have provided mechanistic insights into the genesis of impaired mitochondria in sIBM. This article reviews the disease hallmarks of sIBM, the plausible contributors of mitochondrial damage in the sIBM muscle, and the immunological responses associated with mitochondrial perturbations. Additionally, the potential application of mitochondrial-targeted chemicals as a new treatment strategy to sIBM is explored and discussed.

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Section: Targeting Mitochondrial Health As a New Treatment Strategy O...mentioning

confidence: 99%

Mitochondrial defects in sporadic inclusion body myositis—causes and consequences

Iu,

So,

Chan

2024

Front. Cell Dev. Biol.

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“…The importance of mitochondrial dysfunction in the pathogenesis of AD has prompted the exploration of new treatment strategies designed to improve mitochondrial function [178][179][180]. A major focus has been on correcting oxidative stress imbalances using mitochondrial-targeted antioxidant therapies, and many studies have been conducted in rodent models showing efficacy [181][182][183].…”

Section: Mitochondria In the Treatment Of Admentioning

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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Exploring the Therapeutic Potential of BBB‐Penetrating Phytochemicals With p38 MAPK Modulatory Activity in Addressing Oxidative Stress‐Induced Neurodegenerative Disorders, With a Focus on Alzheimer's Disease

Hosseini,

Sheibani,

Valipour

2024

Phytotherapy Research

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Oxidative stress plays an important role in the occurrence of neurodegenerative diseases. Previous studies indicate a strong connection between oxidative stress, inappropriate activation of the p38 MAPK signaling pathway, and the pathogenesis of neurodegenerative diseases. Although antioxidant therapy is a valid strategy to alleviate these problems, the most important limitation of this approach is the ineffectiveness of drug administration due to the limited permeability of the BBB. Therefore, BBB‐penetrating p38 MAPK modulators with proper antioxidant capacity could be useful in preventing/reducing the complications of neurodegenerative disorders. The current manuscript aims to review the therapeutic capabilities of some recently reviewed naturally occurring p38 MAPK inhibitors in the management of neurodegenerative problems such as Alzheimer's disease. In data collection, we tried to use more recent studies published in high‐quality journals indexed in databases Scopus, Web of Science, PubMed, and so on, but no specific time frame was considered due to the nature of the study. Our evaluations indicate that natural compounds tanshinones, protoberberines, pinocembrin, osthole, rhynchophylline, oxymatrine, schisandrin, piperine, paeonol, ferulic acid, 6‐gingerol, obovatol, and trolox have significant potential for use as supplements/adjuvants in the reduction of neurodegenerative‐related problems. Our findings emphasize the usefulness of BBB‐penetrating phytochemicals with p38 MAPK modulatory activity as potential therapeutic options against neurodegenerative disorders. Of course, the proper use of these compounds depends on considering their toxicity/safety profile and pharmacokinetic characteristics as well as the clinical conditions of users.

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The Natural Alkaloid Palmatine Selectively Induces Mitophagy and Restores Mitochondrial Function in an Alzheimer’s Disease Mouse Model

Cited by 8 publications

References 58 publications

Mitochondrial defects in sporadic inclusion body myositis—causes and consequences

Mitochondrial defects in sporadic inclusion body myositis—causes and consequences

Mitochondria in Alzheimer’s Disease Pathogenesis

Exploring the Therapeutic Potential of BBB‐Penetrating Phytochemicals With p38 MAPK Modulatory Activity in Addressing Oxidative Stress‐Induced Neurodegenerative Disorders, With a Focus on Alzheimer's Disease

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