S6K/p70S6K1 protects against tau-mediated neurodegeneration by decreasing the level of tau phosphorylated at Ser262 in a Drosophila model of tauopathy

Chiku, Tomoki; Motoki, Hayashishita; Saito, Taro; Oka, Mikiko; Shinno, Kanako; Ohtake, Yosuke; Shimizu, Sawako; Asada, Akiko; Hisanaga, Shin‐ichi; Iijima, Koichi; Ando, Kanae

doi:10.1016/j.neurobiolaging.2018.07.021

Cited by 8 publications

(5 citation statements)

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“…44 Consistently, in fly photoreceptors overexpressing tau protein, enhancing autophagy by rapamycin treatment and Atg1 overexpression ameliorated the deformities of ommatidia. [6][7][8] In contrast, evidence of autophagic neuronal death has also been reported in AD fly models. The argument that autophagy contributes to the proteotoxicity of Aβ is exemplified as RNAi knockdown of Atg5 and Atg12 were found to reduce the accumulation of Aβ42.…”

Section: Alzheimer's Diseasementioning

confidence: 99%

Drosophila as a model to study autophagy in neurodegenerative diseases and digestive tract

et al. 2021

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Autophagy regulates cellular homeostasis by degrading and recycling cytosolic components and damaged organelles. Disruption of autophagic flux has been shown to induce or facilitate neurodegeneration and accumulation of autophagic vesicles is overt in neurodegenerative diseases. The fruit fly Drosophila has been used as a model system to identify new factors that regulate physiology and disease. Here we provide a historical perspective of how the fly models have offered mechanistic evidence to understand the role of autophagy in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Charcot-Marie-Tooth neuropathy, and polyglutamine disorders. Autophagy also plays a pivotal role in maintaining tissue homeostasis and protecting organism health. The gastrointestinal tract regulates organism health by modulating food intake, energy balance, and immunity. Growing evidence is strengthening the link between autophagy and digestive tract health in recent years. Here, we also discuss how the fly models have advanced the understanding of digestive physiology regulated by autophagy.

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Section: Alzheimer's Diseasementioning

confidence: 99%

Drosophila as a model to study autophagy in neurodegenerative diseases and digestive tract

et al. 2021

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“…On the other hand, a wide range of tau species can be degraded by autophagy. Induction of autophagy reduces the levels of tau phosphorylated at S262/356 that are not directed to proteasome [38,36]. Dolan et al demonstrated that tau truncated at D421 is predominantly degraded by autophagy, while full-length tau is more prone to proteasomal degradation [39].…”

Section: Autophagy-mediated Degradation Of Taumentioning

confidence: 99%

Section: Tau Phosphorylation In Physiology and Diseasementioning

confidence: 99%

Tau Abnormalities and Autophagic Defects in Neurodegenerative Disorders; A Feed-forward Cycle

Samimi

Asada

Ando

2020

GMJ

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Abnormal deposition of misfolded proteins is a neuropathological characteristic shared by many neurodegenerative disorders including Alzheimer’s disease (AD). Generation of excessive amounts of aggregated proteins and impairment of degradation systems for misfolded proteins such as autophagy can lead to accumulation of proteins in diseased neurons. Molecules that contribute to both these effects are emerging as critical players in disease pathogenesis. Furthermore, impairment of autophagy under disease conditions can be both a cause and a consequence of abnormal protein accumulation. Specifically, disease-causing proteins can impair autophagy, which further enhances the accumulation of abnormal proteins. In this short review, we focus on the relationship between the microtubule-associated protein tau and autophagy to highlight a feed-forward mechanism in disease pathogenesis. [GMJ.2020;9:e1681]

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Section: Autophagy-mediated Degradation Of Taumentioning

confidence: 99%

“…Upregulation of the mTOR pathway not only downregulates autophagy but also elevates phosphorylation of tau via GSK-3β [46]. S6K downstream of mTOR also phosphorylates tau or affects degradation of tau; however, its roles in accumulation of tau remain controversial [32,38]. Lithium is a well-known GSK-3β inhibitor and stimulates autophagy through the inositol signaling pathway [47].…”

Section: Mechanisms That Regulate Both the Generation Of Neurotoxic T...mentioning

confidence: 99%

Tau Abnormalities and Autophagic Defects in Neurodegenerative Disorders; A Feed-forward Cycle

Samimi,

Asada,

Ando

2020

GMJ

View full text Add to dashboard Cite

Abnormal deposition of misfolded proteins is a neuropathological characteristic shared by many neurodegenerative disorders including Alzheimerâ€™s disease (AD). Generation of excessive amounts of aggregated proteins and impairment of degradation systems for misfolded proteins such as autophagy can lead to accumulation of proteins in diseased neurons. Molecules that contribute to both these effects are emerging as critical players in disease pathogenesis. Furthermore, impairment of autophagy under disease conditions can be both a cause and a consequence of abnormal protein accumulation. Specifically, disease-causing proteins can impair autophagy, which further enhances the accumulation of abnormal proteins. In this short review, we focus on the relationship between the microtubule-associated protein tau and autophagy to highlight a feed-forward mechanism in disease pathogenesis. [GMJ.2020;9:e1681]

show abstract

S6K/p70S6K1 protects against tau-mediated neurodegeneration by decreasing the level of tau phosphorylated at Ser262 in a Drosophila model of tauopathy

Cited by 8 publications

References 57 publications

Drosophila as a model to study autophagy in neurodegenerative diseases and digestive tract

Drosophila as a model to study autophagy in neurodegenerative diseases and digestive tract

Tau Abnormalities and Autophagic Defects in Neurodegenerative Disorders; A Feed-forward Cycle

Tau Abnormalities and Autophagic Defects in Neurodegenerative Disorders; A Feed-forward Cycle

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