Role of microtubule-associated protein tau phosphorylation in Alzheimer’s disease

Ma, Rong-Hong; Zhang, Yao; Hong, Xiao‐Yue; Zhang, Junfei; Wang, Jian‐Zhi; Liu, Gong‐Ping

doi:10.1007/s11596-017-1732-x

Cited by 53 publications

(39 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This indicates activation of inflammation in the hippocampus may induce excessive PTP1B production in mice displaying cognitive impairment. PTP1B can inhibit insulin signaling via the pIRS-pAKT-pGSK3β pathway [16,17] and induce Tau phosphorylation, disrupting synapse formation, and maintenance [64,65]. In the present study, we found that dietary MACs downregulated PTP1B expression, improved insulin signaling, and inhibited Tau over-phosphorylation in the hippocampus.…”

Section: Discussionsupporting

confidence: 60%

Supplement of microbiota-accessible carbohydrates prevents neuroinflammation and cognitive decline by improving the gut microbiota-brain axis in diet-induced obese mice

Shi

Wang

Zheng

et al. 2020

J Neuroinflammation

View full text Add to dashboard Cite

Background: Western pattern diets induce neuroinflammation and impair cognitive behavior in humans and animals. Neuroinflammation and cognitive impairment have been associated with microbiota dysbiosis, through the gut-brain axis. Furthermore, microbiota-accessible carbohydrates (MACs) found in dietary fiber are important in shaping the microbial ecosystem and have the potential to improve the gut-brain-axis. However, the effects of MACs on neuroinflammation and cognition in an obese condition have not yet been investigated. The present study aimed to evaluate the effect of MACs on the microbiota-gut-brain axis and cognitive function in obese mice induced by a high-fat and fiber deficient (HF-FD) diet. Methods: C57Bl/6 J male mice were fed with either a control HF-FD or a HF-MAC diet for 15 weeks. Moreover, an additional group was fed with the HF-MAC diet in combination with an antibiotic cocktail (HF-MAC + AB). Following the 15-week treatment, cognitive behavior was investigated; blood, cecum content, colon, and brain samples were collected to determine metabolic parameters, endotoxin, gut microbiota, colon, and brain pathology.

show abstract

Section: Discussionsupporting

confidence: 60%

Supplement of microbiota-accessible carbohydrates prevents neuroinflammation and cognitive decline by improving the gut microbiota-brain axis in diet-induced obese mice

Shi

Wang

Zheng

et al. 2020

J Neuroinflammation

View full text Add to dashboard Cite

show abstract

“…In the present study, dietary β-glucan constrained microglia activation and reduced neuroinflammation in the hippocampus, suggesting enhancement of intestinal barrier function and reduction of LPS translocation might then be critical in β-glucan's beneficial effects on the inflammatory cascade in the hippocampus. Pro-inflammatory cytokines, such as TNFα, increase PTP1B transcription [10], block insulin signalling pIRS-pAKT-pGSK3β for synaptogenesis [11][12][13] and induce Tau phosphorylation, disrupting synapse formation and maintenance [36,37]. We found that chronic β-glucan supplementation down-regulated PTP1B, Synaptic ultrastructural plasticity is important for synaptic functional plasticity.…”

Section: Discussionmentioning

confidence: 71%

β-glucan attenuates cognitive impairment via the gut-brain axis in diet-induced obese mice

Shi

New

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: “Western” style dietary patterns are characterised by a high proportion of highly processed foods rich in fat and low in fibre. This diet-pattern is associated with myriad metabolic dysfunctions including neuroinflammation and cognitive impairment. β-glucan, the major soluble fibre in oat and barley grains, are fermented in the lower gastrointestinal tract, potentially impacting the microbial ecosystem and thus may improve elements of the gut-brain axis. The present study aimed to evaluate the effect of β-glucan on the microbiota-gut-brain axis and cognitive function in an obese mouse model induced by a high-fat and fibre deficient diet (HFFD). Results: After chronic supplementation for 15 weeks, β-glucan prevented HFFD diet-induced cognitive impairment assessed behaviourally by object location and nesting building tests. In the hippocampus, β-glucan countered the HFFD-induced microglia activation and its engulfment of synaptic puncta, and up-regulation of proinflammatory cytokine (TNF-α, IL-1β and IL-6) mRNA expression. Also in the hippocampus, β-glucan significantly promoted PTP1B-IRS-pAKT-pGSK3β-pTau signalling for synaptogenesis; improved the synaptic ultrastructure examined by transmission electron microscopy and increased both pre- and post-synaptic protein levels compared to the HFFD-treated group. In the colon, β-glucan reversed HFFD-induced gut barrier dysfunction: increased the thickness of colonic mucus (Alcian blue and mucin-2 glycoprotein immunofluorescence staining); increased the levels of tight junction proteins occludin and zonula occludens-1; and attenuated bacterial endotoxin translocation. The HFFD diet resulted in widespread microbiota dysbiosis, effects abrogated by chronic β-glucan supplementation, with the β-glucan effects on bacteroidetes and its lower taxa particularly striking. Importantly, acute study of β-glucan supplementation for 7 days demonstrated pronounced, rapid differentiating microbiota changes before the cognitive improvement, suggesting the possible causality of gut microbiota profile on cognition. In support, broad-spectrum antibiotic intervention to severely deplete gut microbiota colonisation, eliminated β-glucan’s effects on improving cognition, highlighting the role of gut microbiota to mediate cognitive behavior. Conclusion: This study provides the first evidence that β-glucan improves indices of cognition and brain function with major beneficial effects all along the gut microbiota-brain axis. Our data suggest that elevating consumption of β-glucan-rich foods is an easily implementable nutritional strategy to alleviate detrimental features of gut-brain dysregulation and prevent neurodegenerative diseases associated with Westernized dietary patterns.

show abstract

“…As one of the mechanisms to drive tau aggregation aberrant phosphorylation has been assumed, since hyperphosphorylation and aggregation of tau are both increased in AD [ 65 ]. Hyperphosphorylation of tau is most likely to result from an imbalance in the activities of specific tau kinases and phosphatases, causing an increased rate of tau phosphorylation and/ or decreased rate of de-phosphorylation [ 66 ]. Consequently, tau hyperphosphorylation reduces its binding affinity to microtubules, thereby induces a loss of tau’s normal microtubule-stabilizing function [ 67 , 68 ], and thus causes microtubule depolymerization [ 49 ].…”

Section: Tau Proteinmentioning

confidence: 99%

Insights into Disease-Associated Tau Impact on Mitochondria

Szabo

Eckert

Grimm

2020

IJMS

View full text Add to dashboard Cite

Abnormal tau protein aggregation in the brain is a hallmark of tauopathies, such as frontotemporal lobar degeneration and Alzheimer’s disease. Substantial evidence has been linking tau to neurodegeneration, but the underlying mechanisms have yet to be clearly identified. Mitochondria are paramount organelles in neurons, as they provide the main source of energy (adenosine triphosphate) to these highly energetic cells. Mitochondrial dysfunction was identified as an early event of neurodegenerative diseases occurring even before the cognitive deficits. Tau protein was shown to interact with mitochondrial proteins and to impair mitochondrial bioenergetics and dynamics, leading to neurotoxicity. In this review, we discuss in detail the different impacts of disease-associated tau protein on mitochondrial functions, including mitochondrial transport, network dynamics, mitophagy and bioenergetics. We also give new insights about the effects of abnormal tau protein on mitochondrial neurosteroidogenesis, as well as on the endoplasmic reticulum-mitochondria coupling. A better understanding of the pathomechanisms of abnormal tau-induced mitochondrial failure may help to identify new targets for therapeutic interventions.

show abstract

Role of microtubule-associated protein tau phosphorylation in Alzheimer’s disease

Cited by 53 publications

References 66 publications

Supplement of microbiota-accessible carbohydrates prevents neuroinflammation and cognitive decline by improving the gut microbiota-brain axis in diet-induced obese mice

Supplement of microbiota-accessible carbohydrates prevents neuroinflammation and cognitive decline by improving the gut microbiota-brain axis in diet-induced obese mice

β-glucan attenuates cognitive impairment via the gut-brain axis in diet-induced obese mice

Insights into Disease-Associated Tau Impact on Mitochondria

Contact Info

Product

Resources

About