Tau in Alzheimer’s Disease: Pathological Alterations and an Attractive Therapeutic Target

Gu, Jianlan; Liu, Fei

doi:10.1007/s11596-020-2282-1

Cited by 18 publications

(7 citation statements)

References 162 publications

(198 reference statements)

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“…744 Tau is the major microtubule-associated protein of a mature neuron, and it is a central molecule in the pathogenesis of AD. 745 Previous studies have highlighted the importance of PTMs (e.g., O-GlcNAcylation, phosphorylation, and acetylation) of Tau in AD. [746][747][748] For example, the level of O-GlcNAcylation of tau in AD brain is reduced, and SIRT1 reduces O-GlcNAcylation of tau through CREB.…”

Section: ) Other Intestinal Diseasesmentioning

confidence: 99%

The sirtuin family in health and disease

Zhang

Chen

et al. 2022

Sig Transduct Target Ther

229

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Sirtuins (SIRTs) are nicotine adenine dinucleotide(+)-dependent histone deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes, and are involved in numerous biological processes. Currently, seven mammalian homologs of yeast Sir2 named SIRT1 to SIRT7 have been identified. Increasing evidence has suggested the vital roles of seven members of the SIRT family in health and disease conditions. Notably, this protein family plays a variety of important roles in cellular biology such as inflammation, metabolism, oxidative stress, and apoptosis, etc., thus, it is considered a potential therapeutic target for different kinds of pathologies including cancer, cardiovascular disease, respiratory disease, and other conditions. Moreover, identification of SIRT modulators and exploring the functions of these different modulators have prompted increased efforts to discover new small molecules, which can modify SIRT activity. Furthermore, several randomized controlled trials have indicated that different interventions might affect the expression of SIRT protein in human samples, and supplementation of SIRT modulators might have diverse impact on physiological function in different participants. In this review, we introduce the history and structure of the SIRT protein family, discuss the molecular mechanisms and biological functions of seven members of the SIRT protein family, elaborate on the regulatory roles of SIRTs in human disease, summarize SIRT inhibitors and activators, and review related clinical studies.

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Section: ) Other Intestinal Diseasesmentioning

confidence: 99%

The sirtuin family in health and disease

Zhang

Chen

et al. 2022

Sig Transduct Target Ther

229

View full text Add to dashboard Cite

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“…This mechanism was described for axonal microtubules in cultured neurons and seems to be essential for axonal transport [ 68 , 71 , 75 ]. Moreover, this region also interacts with other proteins, such as actin or heat shock proteins [ 76 , 77 ]. Due to its interaction with microtubules, Tau is a modulator in a number of cellular processes involving cytoskeletal structure, such as morphogenesis, cellular division, and intracellular trafficking of organelles and vesicles [ 68 , 69 ].…”

Section: Tau Isoformsmentioning

confidence: 99%

Tau Isoforms: Gaining Insight into MAPT Alternative Splicing

Corsi

Bombieri

Valenti

2022

IJMS

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Tau microtubule-associated proteins, encoded by the MAPT gene, are mainly expressed in neurons participating in axonal transport and synaptic plasticity. Six major isoforms differentially expressed during cell development and differentiation are translated by alternative splicing of MAPT transcripts. Alterations in the expression of human Tau isoforms and their aggregation have been linked to several neurodegenerative diseases called tauopathies, including Alzheimer’s disease, progressive supranuclear palsy, Pick’s disease, and frontotemporal dementia with parkinsonism linked to chromosome 17. Great efforts have been dedicated in recent years to shed light on the complex regulatory mechanism of Tau splicing, with a perspective to developing new RNA-based therapies. This review summarizes the most recent contributions to the knowledge of Tau isoform expression and experimental models, highlighting the role of cis-elements and ribonucleoproteins that regulate the alternative splicing of Tau exons.

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“…In our study, we found memory impairment was induced in STZ‐induced model according to the Morris water maze test, and PTS protected mice against memory deficit, which was consistent with a previous research (Meng et al, 2019). Aβ accumulation and hyperphosphorylated Tau are two cardinal pathological hallmarks of AD, which might be related to neuronal dysfunction and cognitive decline (Gu & Liu, 2020; Yu & Wu, 2021). Here we found that PTS weakened Aβ 1–42 accumulation and Tau hyperphosphorylation in AD mice, indicating that PTS might regulate Aβ and Tau pathology to inhibit AD progression.…”

Section: Discussionmentioning

confidence: 99%

Protective effect of pterostilbene in a streptozotocin‐induced mouse model of Alzheimer's disease by targeting monoamine oxidase B

Tian

et al. 2022

J of Applied Toxicology

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Alzheimer's disease (AD) is a neurodegenerative disease in elderly population. Pterostilbene (PTS) is a resveratrol analog with neuroprotective activity. However, the biological mechanisms of PTS in AD progression are largely uncertain. An animal model of AD was established using streptozotocin (STZ)-treated C57BL/6J mice. Monoamine oxidase B (MAOB) expression was analyzed by bioinformatics analysis and detected by western blotting assay. The memory impairment was investigated by Morris water maze test. The levels of Tau hyperphosphorylation and death-related proteins were detected by western blotting analysis. The levels of amyloid β (Aβ) 1-42 accumulation, oxidative stress-related markers (ROS, MDA, SOD, and GSH), and inflammation-relative markers (TNF-α, IL-1β, IL-6, and p-NF-κB) were measured by ELISA. MAOB expression was increased in hippocampus of AD mice, and it was decreased by PTS. PTS attenuated STZ-induced body weight loss and memory impairment by regulating MAOB. PTS mitigated Aβ 1-42 accumulation and Tau hyperphosphorylation by regulating MAOB in STZ-treated mice. PTS attenuated neuronal death by decreasing cleaved caspase-3 and Bax levels and increasing Bcl2 expression in hippocampus by regulating MAOB in STZ-treated mice. PTS weakened STZ-induced oxidative stress in hippocampus by decreasing ROS and MDA levels and increasing SOD and GSH levels by regulating MAOB. PTS protected against STZ-induced neuroinflammation in hippocampus by inhibiting TNF-α, IL-1β, IL-6, and p-NF-κB levels through regulating MAOB. In conclusion, PTS alleviates STZ-induced memory impairment, Aβ

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Tau in Alzheimer’s Disease: Pathological Alterations and an Attractive Therapeutic Target

Cited by 18 publications

References 162 publications

The sirtuin family in health and disease

The sirtuin family in health and disease

Tau Isoforms: Gaining Insight into MAPT Alternative Splicing

Protective effect of pterostilbene in a streptozotocin‐induced mouse model of Alzheimer's disease by targeting monoamine oxidase B

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