Clemastine fumarate attenuates tauopathy and meliorates cognition in hTau mice via autophagy enhancement

Zhu, Jiahui; Jiang, Xingjun; Chang, Yanmin; Wu, Yanqing; Sun, Shangqi; Wang, Cailin; Zheng, Shuang; Wang, Min; Yao, Yunpeng; Li, Gang; Ma, Rong

doi:10.1016/j.intimp.2023.110649

Cited by 2 publications

(2 citation statements)

References 53 publications

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“…It has been highlighted that MAP1LC3B/LC3-associated phagocytosis is closely linked to amyloid β clearance ( Lee et al, 2019 ). Consistently, autophagy enhancement promotes the degradation of Tau protein, thereby alleviating Tauopathy-related neuroinflammation and synapse loss to restore cognition ( Zhu et al, 2023 ). Importantly, mitophagy maintains a balanced mitochondrial homeostasis via removal of the accumulated ROS and toxic fragments.…”

Section: Clinical Prospectivementioning

confidence: 99%

The role of Foxo3a in neuron-mediated cognitive impairment

Liu,

Wu,

Wang

et al. 2024

Front. Mol. Neurosci.

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Cognitive impairment (COI) is a prevalent complication across a spectrum of brain disorders, underpinned by intricate mechanisms yet to be fully elucidated. Neurons, the principal cell population of the nervous system, orchestrate cognitive processes and govern cognitive balance. Extensive inquiry has spotlighted the involvement of Foxo3a in COI. The regulatory cascade of Foxo3a transactivation implicates multiple downstream signaling pathways encompassing mitochondrial function, oxidative stress, autophagy, and apoptosis, collectively affecting neuronal activity. Notably, the expression and activity profile of neuronal Foxo3a are subject to modulation via various modalities, including methylation of promoter, phosphorylation and acetylation of protein. Furthermore, upstream pathways such as PI3K/AKT, the SIRT family, and diverse micro-RNAs intricately interface with Foxo3a, engendering alterations in neuronal function. Through several downstream routes, Foxo3a regulates neuronal dynamics, thereby modulating the onset or amelioration of COI in Alzheimer’s disease, stroke, ischemic brain injury, Parkinson’s disease, and traumatic brain injury. Foxo3a is a potential therapeutic cognitive target, and clinical drugs or multiple small molecules have been preliminarily shown to have cognitive-enhancing effects that indirectly affect Foxo3a. Particularly noteworthy are multiple randomized, controlled, placebo clinical trials illustrating the significant cognitive enhancement achievable through autophagy modulation. Here, we discussed the role of Foxo3a in neuron-mediated COI and common cognitively impaired diseases.

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Section: Clinical Prospectivementioning

confidence: 99%

The role of Foxo3a in neuron-mediated cognitive impairment

Liu,

Wu,

Wang

et al. 2024

Front. Mol. Neurosci.

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“…Tau protein is effectively degraded through autophagy, which in turn regulates autophagy (Zhu et al, 2023a). Some studies have shown that autophagy de cient mice show hyperphosphorylation of Tau protein, while when autophagy resumes, the phosphorylated Tau protein decreases (Uddin et al, 2019a;Fairley et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

Quercetin improves homocysteine-induced learning and memory impairment in rats via AMPK/mTOR

Gong,

Xu,

et al. 2024

Preprint

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Alzheimer's disease (AD) is a progressive neurodegenerative brain disease. At present, the main treatment strategy is to alleviate certain symptoms, but the potential mechanisms of AD are not fully understood, and there is a lack of effective treatment methods in clinical practice. Quercetin (QT) can significantly protect neurodegeneration by inhibiting oxidative stress and inflammation, and has the potential to play a greater role in clinical practice. Therefore, this study aims to explore the potential mechanism of QT based on the AMPK/mTOR pathway in improving the learning and memory abilities of AD rats.For this purpose,we established an AD rat model by injecting Hcy into the tail vein.After successful model validation, Quercetin and AMPK inhibitor were gavaged.Then, the role of the AMPK/mTOR pathway in QT protected nerve regeneration was determined using Morris water maze, Nissl staining, Western blot and immunohistochemistry.We observed that QT significantly improved the learning and memory abilities in rat models with AD, as demonstrated by the short learning latency and greater times of travel across the platform. Nissl staining showed that QT could reduce neurological Apoptosis and amenorrate neurological implementation .Western blot and immunohistochemistry staining showed that questionnaire significantly increased p-AMPK, while reducing p-mTOR and p-Tau .In addition, the application of specific AMPK inhibitor can effectively reverse these changes, further enhancing the improvement effect of QT inhibition on AD, Thereby improving the learning and memory improvement induced by Hcy in AD model rates, and thus improving learning and memory abilities.

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Clemastine fumarate attenuates tauopathy and meliorates cognition in hTau mice via autophagy enhancement

Cited by 2 publications

References 53 publications

The role of Foxo3a in neuron-mediated cognitive impairment

The role of Foxo3a in neuron-mediated cognitive impairment

Quercetin improves homocysteine-induced learning and memory impairment in rats via AMPK/mTOR

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