Strain-specific clearance of seed-dependent tau aggregation by lithium-induced autophagy

Uddin, Mohammad Nasir; Elahi, Montasir; Shimonaka, Shotaro; Kakuta, Soichiro; Ishiguro, Koichi; Motoi, Yumiko

doi:10.1016/j.bbrc.2020.12.113

Cited by 7 publications

(4 citation statements)

References 29 publications

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“…Lithium has been shown to induce clearance of α-synuclein aggregate or mutant Huntingtin ( Sarkar et al, 2005 ). A recent paper showed the effect of lithium in the clearance of Tau aggregate ( Uddin et al, 2021 ).…”

Section: Autophagy Modulators In Other Diseasesmentioning

confidence: 99%

Current Status of Autophagy Enhancers in Metabolic Disorders and Other Diseases

Park

Lee

2022

Front. Cell Dev. Biol.

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Autophagy is pivotal in the maintenance of organelle function and intracellular nutrient balance. Besides the role of autophagy in the homeostasis and physiology of the individual tissues and whole organism in vivo, dysregulated autophagy has been incriminated in the pathogenesis of a variety of diseases including metabolic diseases, neurodegenerative diseases, cardiovascular diseases, inflammatory or immunological disorders, cancer and aging. Search for autophagy modulators has been widely conducted to amend dysregulation of autophagy or pharmacologically modulate autophagy in those diseases. Current data support the view that autophagy modulation could be a new modality for treatment of metabolic syndrome associated with lipid overload, human-type diabetes characterized by deposition of islet amyloid or other diseases including neurodegenerative diseases, infection and cardiovascular diseases. While clinically available bona fide autophagy modulators have not been developed yet, it is expected that on-going investigation will lead to the development of authentic autophagy modulators that can be safely administered to patients in the near future and will open a new horizon for treatment of incurable or difficult diseases.

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Section: Autophagy Modulators In Other Diseasesmentioning

confidence: 99%

Current Status of Autophagy Enhancers in Metabolic Disorders and Other Diseases

Park

Lee

2022

Front. Cell Dev. Biol.

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“…In an in vitro study, researchers used human tauopathy brain extracts as a seed to induce similar tau aggregation in the cell model. The results show that lithium reduces insoluble tau and p62 levels and increases autophagic vacuoles and the LC3-II protein level 195 . In transgenic mice overexpressing human mutant tau, oral lithium for 4 months can reduce the levels of hyperphosphorylated and aggregated tau, decrease the number of neurofibrillary tangles, and attenuate movement disorders.…”

Section: Autophagy Modulators For Ad Therapymentioning

confidence: 86%

Pharmacological modulation of autophagy for Alzheimer's disease therapy: Opportunities and obstacles

Deng

Dong

Zhou

et al. 2022

Acta Pharmaceutica Sinica B

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“…Notably, the mTOR inhibitor rapamycin has been found to increase autophagy levels, reduce amyloid-beta and phosphorylated tau levels, and improve cognition in AD mouse models (Yang and Zhang, 2020). Lithium's similar enhancement of autophagy and attenuation of amyloid-beta and tau pathology enhances its therapeutic potential for AD (Morris and Berk, 2016;Uddin et al, 2021).…”

Section: Therapeutic Potential Of Modulating Autophagymentioning

confidence: 99%

Proteostasis and neurodegeneration: a closer look at autophagy in Alzheimer's disease

Barmaki,

Nourazarian,

Khaki-Khatibi

2023

Front. Aging Neurosci.

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Alzheimer's disease (AD) is characterized by the accumulation of misfolded amyloid-beta and tau proteins. Autophagy acts as a proteostasis process to remove protein clumps, although it progressively weakens with aging and AD, thus facilitating the accumulation of toxic proteins and causing neurodegeneration. This review examines the impact of impaired autophagy on the progression of AD disease pathology. Under normal circumstances, autophagy removes abnormal proteins and damaged organelles, but any dysfunction in this process can lead to the exacerbation of amyloid and tau pathology, particularly in AD. There is increasing attention to therapeutic tactics to revitalize autophagy, including reduced caloric intake, autophagy-stimulating drugs, and genetic therapy. However, the translation of these strategies into clinical practice faces several hurdles. In summary, this review integrates the understanding of the intricate role of autophagy dysfunction in Alzheimer's disease progression and reinforces the promising prospects of autophagy as a beneficial target for treatments to modify the course of Alzheimer's disease.

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Strain-specific clearance of seed-dependent tau aggregation by lithium-induced autophagy

Cited by 7 publications

References 29 publications

Current Status of Autophagy Enhancers in Metabolic Disorders and Other Diseases

Current Status of Autophagy Enhancers in Metabolic Disorders and Other Diseases

Pharmacological modulation of autophagy for Alzheimer's disease therapy: Opportunities and obstacles

Proteostasis and neurodegeneration: a closer look at autophagy in Alzheimer's disease

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