Cornel Iridoid Glycoside Protects Against STAT1-Dependent Synapse and Memory Deficits by Increasing N-Methyl-D-aspartate Receptor Expression in a Tau Transgenic Mice

Ma, Denglei; Huang, Rui; Guo, Kaiwen; Zhao, Zirun; Wei, Weipeng; Gu, Li-Hong; Li, Lin; Zhang, Lan

doi:10.3389/fnagi.2021.671206

Cited by 10 publications

(9 citation statements)

References 34 publications

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“…For example, our data highlight that immunoreactivity of the widely-used T22 antibody clone is not restricted solely to oligomeric Tau, since it also detected monomeric Tau on WBs. This feature was evident in several previous studies but had not been emphasised ( [162], Fig. 4; [163], Fig.…”

Section: Antibody Performance: Ability To Detect the Target Protein A...mentioning

confidence: 68%

Validation of Tau Antibodies for Use in Western Blotting and Immunohistochemistry

Ellis

Lekka

Tulmin

et al. 2023

Preprint

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BackgroundThe microtubule-associated protein Tau has attracted diverse and increasing research interest, with Tau being mentioned in the title/abstract of nearly 34,000 PubMed-indexed publications to date. To accelerate studies into Tau biology, the characterisation of its multiple proteoforms, including disease-relevant post-translational modifications (PTMs), and its role in neurodegeneration, a multitude of Tau-targeting antibodies have been developed, with hundreds of distinct antibody clones currently available for purchase. Nonetheless, concerns over antibody specificity and limited understanding of the performance of many of these reagents has hindered research.MethodsWe have employed a range of techniques in combination with samples of murine and human origin to characterise the performance and specificity of 53 commercially-available Tau antibodies by Western blot, and a subset of these, 35 antibodies, in immunohistochemistry.ResultsContinued expression of residual protein was found in presumptive Tau “knockout” human cells and further confirmed through mass-spectrometry proteomics, providing evidence of Tau isoforms generated by exon skipping. Importantly, many total and isoform-specific antibodies failed to detect this residual Tau, as well as Tau expressed at low, endogenous levels, thus highlighting the importance of antibody choice. Our data further reveal that the binding of several “total” Tau antibodies, which are assumed to detect Tau independently of post-translational modifications, was partially inhibited by phosphorylation. Many antibodies also displayed non-specific cross-reactivity, with some total and phospho-Tau antibodies cross-reacting with MAP2 isoforms, while the “oligomer-specific” T22 antibody detected monomeric Tau on Western blot. Regardless of their specificity, with one exception, the phospho-Tau antibodies tested were found to not detect the unphosphorylated protein.ConclusionsWe identify Tau antibodies across all categories (total, PTM-dependent and isoform-specific) that can be employed in Western blot and/or immunohistochemistry applications to reliably detect even low levels of Tau expression with high specificity. This is of particular importance for studying Tau in non-neuronal cells and peripheral tissues, as well as for the confident validation of knockout cells and/or animal models. This work represents an extensive resource that serves as a point of reference for future studies. Our findings may also aid in the re-interpretation of existing data and improve reproducibility of Tau research.

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Section: Antibody Performance: Ability To Detect the Target Protein A...mentioning

confidence: 68%

Validation of Tau Antibodies for Use in Western Blotting and Immunohistochemistry

Ellis

Lekka

Tulmin

et al. 2023

Preprint

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“…Fructose Corni iridoid glycoside (CIG), the active ingredient of Fructose Corni, improves exercise capacity; attenuates neuronal loss or demyelination; increases the expression of synaptophysin, postsynaptic density protein 95 (PSD-95) and AMPA receptor subunit 1; increases the level of soluble APPα fragment and a disintegrin and metalloproteinase 10 (ADAM10); and decreases receptor-interacting protein kinase-1 (RIPK1) and mixed lineage kinase domain-like protein (MLKL) levels in the brains of SAMP8 mice (Ma et al, 2021a). P301S transgenic mice, an animal model of tauopathy and AD, exhibit tau pathology and synaptic dysfunction.…”

Section: Fructose Cornimentioning

confidence: 99%

“…In this model, CIG improves cognitive impairment and survival rates. The main mechanism of its involvement in the regulation of synaptic dysfunction is to inhibit the activation of the Janus kinase-2 (JAK2)/signal transducer and activator of transcription 1 (STAT1) signaling pathway ( Ma et al, 2021b ). In APP/PS1/tau triple transgenic AD (3×Tg-AD) model mice, CIG can improve learning and memory impairment by reducing Aβ content and tau hyperphosphorylation and increasing neurotrophic factors in the brain ( Yang C. et al, 2020 ).…”

Section: Single Tcms and Their Active Ingredientsmentioning

confidence: 99%

Research progress in traditional Chinese medicine in the treatment of Alzheimer’s disease and related dementias

Tan

et al. 2022

Front. Pharmacol.

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Alzheimer’s disease (AD) is the world’s leading cause of dementia and has become a huge economic burden on nations and families. However, the exact etiology of AD is still unknown, and there are no efficient medicines or methods to prevent the deterioration of cognition. Traditional Chinese medicine (TCM) has made important contributions in the battle against AD based on the characteristics of multiple targets of TCM. This study reviewed the treatment strategies and new discoveries of traditional Chinese medicine in current research, which may be beneficial to new drug researchers.

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“…officinalis. The anti-inflammatory and antioxidant properties of CIG have been proven to be effective against neurodegenerative diseases. , In particular, we discovered that CIG could regulate calpain expression and activation, attenuate tau protein phosphorylation, and reduce neuronal loss and neuroinflammatory protection in Alzheimer’s disease (AD). , In addition, CIG promotes neurogenesis and angiogenesis and inhibits neuroinflammation and apoptosis in rat brains after focal cerebral ischemia. , However, the specific impact of CIG on neuroinflammation during VaD treatment remains poorly understood. Therefore, this study aims to clarify the influences of CIG on VaD and the underlying mechanisms of molecular intervention that involve the NLRP3/calpain-1 pathway.…”

Section: Introductionmentioning

confidence: 99%

“…25,26 In particular, we discovered that CIG could regulate calpain expression and activation, attenuate tau protein phosphorylation, and reduce neuronal loss and neuroinflammatory protection in Alzheimer's disease (AD). 27,28 In addition, CIG promotes neurogenesis and angiogenesis and inhibits neuroinflammation and apoptosis in rat brains after focal cerebral ischemia. 29,30 However, the specific impact of CIG on neuroinflammation during VaD treatment remains poorly understood.…”

Section: ■ Introductionmentioning

confidence: 99%

Cornel Iridoid Glycoside Alleviates Microglia-Mediated Inflammatory Response via the NLRP3/Calpain Pathway

Zheng

Gao

Zhang

et al. 2022

J. Agric. Food Chem.

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Vascular dementia (VaD) is associated with cerebral hypoperfusion, which results in long-term cognitive impairment and memory loss. Cornel iridoid glycoside (CIG) is the major active constituent isolated from the ripe fruit of Cornus officinalis. Previous studies have shown that CIG enhances neurological function in VaD rats. In the present research, we attempted to clarify the molecular processes underlying the role of CIG in neuroinflammation in VaD. We created a chronic cerebral ischemia rat model by ligation of the bilateral common carotid arteries (2VO) and then treated rats with different concentrations of CIG. Comprehensive analyses revealed that CIG ameliorated myelin integrity and neuronal loss. Furthermore, we also found that CIG inhibited polarized microglia activation and attenuated inflammasome-mediated production of proinflammatory cytokines in BV2 microglia cells induced by LPS/IFN-γ and in the brains of 2VO rats. To further elucidate the role of CIG in microglia-mediated inflammatory response, we investigated the expression and activity of calpain. CIG inhibited the expression and activity of calpain 1/2, which was characterized by decreased calpastatin and spectrin αII expression. In particular, intra- and extracellular calpain 1 levels were reduced by CIG. However, CIG showed weak interaction with calpain 1. In addition, we found that CG administration significantly repressed the assembly of the NOD-like receptor protein 3 (NLRP3) inflammasome, including NLRP3, ASC, and caspase-1. In conclusion, our knowledge of the mechanisms by which CIG regulates NLRP3/calpain signaling to influence inflammatory responses offers further insights into potential therapeutic strategies to treat VaD.

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Cornel Iridoid Glycoside Protects Against STAT1-Dependent Synapse and Memory Deficits by Increasing N-Methyl-D-aspartate Receptor Expression in a Tau Transgenic Mice

Cited by 10 publications

References 34 publications

Validation of Tau Antibodies for Use in Western Blotting and Immunohistochemistry

Validation of Tau Antibodies for Use in Western Blotting and Immunohistochemistry

Research progress in traditional Chinese medicine in the treatment of Alzheimer’s disease and related dementias

Cornel Iridoid Glycoside Alleviates Microglia-Mediated Inflammatory Response via the NLRP3/Calpain Pathway

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