Tau overexpression impairs neuronal endocytosis by decreasing the GTPase dynamin 1 through the miR‐132/MeCP2 pathway

Xie, Ao-Ji; Hou, Tongyao; Xiong, Wei; Huang, He-Zhou; Zheng, Jie; Li, Ké; Man, Heng‐Ye; Hu, Yazhuo; Han, Zhitao; Zhang, Honghong; Wei, Na; Wang, Jian‐Zhi; Liú, Dan; Lu, Youming; Zhu, Ling‐Qiang

doi:10.1111/acel.12929

Cited by 21 publications

(17 citation statements)

References 8 publications

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“…The deregulation of miRNAs has been well validated in AD ( Liu et al, 2017 ; Wang et al, 2018 ; Tang et al, 2019 ; Xie et al, 2019 ; Hou et al, 2020 ). In the present study, we found that miR-144-3p was upregulated in the hippocampi and mPFC of mice with AD.…”

Section: Discussionmentioning

confidence: 99%

Elevated Levels of miR-144-3p Induce Cholinergic Degeneration by Impairing the Maturation of NGF in Alzheimer’s Disease

Zhou

Zhang

Tan

et al. 2021

Front. Cell Dev. Biol.

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Cholinergic degeneration is one of the key pathological hallmarks of Alzheimer’s disease (AD), a condition that is characterized by synaptic disorders and memory impairments. Nerve growth factor (NGF) is secreted in brain regions that receive projections from the basal forebrain cholinergic neurons. The trophic effects of NGF rely on the appropriate maturation of NGF from its precursor, proNGF. The ratio of proNGF/NGF is known to be increased in patients with AD; however, the mechanisms that underlie this observation have yet to be elucidated. Here, we demonstrated that levels of miR-144-3p are increased in the hippocampi and the medial prefrontal cortex of an APP/PS1 mouse model of AD. These mice also exhibited cholinergic degeneration (including the loss of cholinergic fibers, the repression of choline acetyltransferase (ChAT) activity, the reduction of cholinergic neurons, and an increased number of dystrophic neurites) and synaptic/memory deficits. The elevated expression of miR-144-3p specifically targets the mRNA of tissue plasminogen activator (tPA) and reduces the expression of tPA, thus resulting in the abnormal maturation of NGF. The administration of miR-144-3p fully replicated the cholinergic degeneration and synaptic/memory deficits observed in the APP/PS1 mice. The injection of an antagomir of miR-144-3p into the hippocampi partially rescued cholinergic degeneration and synaptic/memory impairments by restoring the levels of tPA protein and by correcting the ratio of proNGF/NGF. Collectively, our research revealed potential mechanisms for the disturbance of NGF maturation and cholinergic degeneration in AD and identified a potential therapeutic target for AD.

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Section: Discussionmentioning

confidence: 99%

Elevated Levels of miR-144-3p Induce Cholinergic Degeneration by Impairing the Maturation of NGF in Alzheimer’s Disease

Zhou

Zhang

Tan

et al. 2021

Front. Cell Dev. Biol.

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“…Therefore, miR-132 plays an important role in the pathogenesis of AD by regulating apoptosis and GTDC-1/CDK-5/tau phosphorylation signaling mechanisms ( Liu and Zhang, 2019 ). Notably, in human tau-overexpressing neurons, methyl-CpG-binding protein 2 (MeCP2) levels were increased, while miR-132 was decreased, and miR-132 was found to negatively regulate MeCP2 expression both in vitro and in vivo ( Xie et al, 2019 ). Xie et al, found that miR-132 deficiency led to increased tau expression, phosphorylation, and aggregation in mice.…”

Section: Neuropathogenesis Of Mir-132 In Admentioning

confidence: 99%

“…Xie et al, found that miR-132 deficiency led to increased tau expression, phosphorylation, and aggregation in mice. In addition, miR-132 regulated tau expression and phosphorylation, and thus contributed to tauopathy in AD by regulating MeCP2 levels, suggesting a vicious cycle of tau-miR-132-MeCP2-tau abnormalities in AD ( Xie et al, 2019 ). Smith et al, found that miR-132 deficiency led to increased tau expression, phosphorylation and aggregation in mice, as well as demonstrating that miR-132 directly targeted tau mRNA to regulate its expression, by using reporter assays and cell-based studies.…”

Section: Neuropathogenesis Of Mir-132 In Admentioning

confidence: 99%

Alzheimer’s Disease and microRNA-132: A Widespread Pathological Factor and Potential Therapeutic Target

Zhang

Bian

2021

Front. Neurosci.

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Alzheimer’s disease (AD) is a common neurodegenerative disease in the elderly and is the most common type of dementia. AD is mostly gradual onset, and involves slow, progressive mental decline, accompanied by personality changes; the incidence of AD gradually increases with age. The etiology of AD is unknown, although it is currently believed to be related to abnormal deposition of amyloid β-protein (Aβ) in the brain, hyperphosphorylation of microtubule-associated protein tau, and the release of various cytokines, complements, activators and chemokines by cells. MicroRNAs (miRNAs) are a class of highly conserved non-coding RNAs that regulate gene expression at the post-transcriptional level, and manipulate the functions of intracellular proteins and physiological processes. Emerging studies have shown that miRNA plays an important role in regulating AD-related genes. MiR-132 is known as “NeurimmiR” due to its involvement in numerous neurophysiological and pathological processes. Accumulating pre-clinical results suggest that miR-132 may be involved in the progression of Aβ and tau pathology. Moreover, clinical studies have indicated that decreased circulating miR-132 levels could be used a potential diagnostic biomarker in AD. Here, we review the pathogenic role of miR-132 activity in AD, and the potential of targeting miR-132 for developing future therapeutic strategies.

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“…An increasing number of miRNAs have emerged as biomarkers for the diagnosis and prognosis of various neurological diseases (Wang et al, ; Xie et al, ). Accumulating data imply that differential miRNA expression profiles detected by sequencing are involved in developing cognitive defects (Tang et al, ) and Parkinson's disease (Su et al, ).…”

Section: Discussionmentioning

confidence: 99%

MiR‐21‐5p/dual‐specificity phosphatase 8 signalling mediates the anti‐inflammatory effect of haem oxygenase‐1 in aged intracerebral haemorrhage rats

Ouyang

Wang

et al. 2019

Aging Cell

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Intracerebral haemorrhage (ICH) is a severe neurological disorder caused by bleeding within the brain tissue. Inflammation has been implicated in ICH pathogenesis and is a potential therapeutic target for ICH. Haemin, an activator of haem oxygenase-1 (HO-1), rapidly increases HO-1 protein expression and activity and has been shown to distinctly affect anti-inflammatory functions after central nervous system (CNS) injury. However, less is known about the mechanisms that underlie the antiinflammatory effects of haemin in aged rats post-ICH. Here, we performed microarray analysis to identify miRNAs that respond strongly to HO-1 regulation in ICH rats and found that miR-21-5p induced the most significant change. Using Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and Gene Ontology (GO) analysis, we focused on dual-specificity phosphatase 8 (DUSP8) from the predicted miR-21-5p targets. Luciferase reporter assays confirmed that miR-21-5p bound directly to DUSP8. MiR-21-5p upregulation in vitro downregulated DUSP8 expression. Importantly, intracerebroventricularly injecting antagomir for miR-21-5p (A-miR-21-5p), which was used to inhibit miR-21-5p in aged ICH rats, significantly reduced the neurological defects, repaired cognitive impairment, alleviated blood-brain barrier (BBB) permeability, inhibited neuronal apoptosis posthaemorrhage and accelerated haematoma absorption. In addition, serum miR-21-5p levels were notably elevated in patients relative to healthy individuals and were correlated with National Institutes of Health Stroke Scale (NIHSS) scores and clinical outcomes. In summary, A-miR-21-5p increased HO-1 expression in cerebral haematomas, thus eliciting the

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Tau overexpression impairs neuronal endocytosis by decreasing the GTPase dynamin 1 through the miR‐132/MeCP2 pathway

Cited by 21 publications

References 8 publications

Elevated Levels of miR-144-3p Induce Cholinergic Degeneration by Impairing the Maturation of NGF in Alzheimer’s Disease

Elevated Levels of miR-144-3p Induce Cholinergic Degeneration by Impairing the Maturation of NGF in Alzheimer’s Disease

Alzheimer’s Disease and microRNA-132: A Widespread Pathological Factor and Potential Therapeutic Target

MiR‐21‐5p/dual‐specificity phosphatase 8 signalling mediates the anti‐inflammatory effect of haem oxygenase‐1 in aged intracerebral haemorrhage rats

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