Zinc binds to and directly inhibits protein phosphatase 2A in vitro

Luo, Danju; Wang, Xiulian; Qiu, Mei; Yang, Yang; Xiong, Yan; Wang, Jian‐Zhi; Ye, Qifa; R, Liu

doi:10.1007/s12264-014-1519-z

Cited by 30 publications

(20 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cations such as zinc and iron are found in the senile plaques in AD brains with high concentrations [74][75][76] . We have reported that zinc inhibits PP2A directly through binding to PP2Ac (51-270) in vitro [77] . Zinc can also induce PP2A phosphorylation at tyrosine 307 (Y307) and lead to tau hyperphosphorylation [78] .…”

Section: Metal Chelatorsmentioning

confidence: 98%

Protein Phosphatase 2A as a Drug Target in the Treatment of Cancer and Alzheimer’s Disease

et al. 2020

Self Cite

View full text Add to dashboard Cite

Protein phosphatase 2A (PP2A) is a major serine/threonine phosphatase which participates in the regulation of multiple cellular processes. As a confirmed tumor suppressor, PP2A activity is downregulated in tumors and its re-activation can induce apoptosis of cancer cells. In the brains of Alzheimer's disease (AD) patients, decreased PP2A activity also plays a key role in promoting tau hyperphosphorylation and Aβ generation. In this review, we discussed compounds aiming at modulating PP2A activity in the treatment of cancer or AD. The upstream factors that inactivate PP2A in diseases have not been fully elucidated and further studies are needed. It will help for the refinement and development of novel and clinically tractable PP2A-targeted compounds or therapies for the treatment of tumor and AD.

show abstract

Section: Metal Chelatorsmentioning

confidence: 98%

Protein Phosphatase 2A as a Drug Target in the Treatment of Cancer and Alzheimer’s Disease

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…By dephosphorylating these key signaling molecules, a number of phosphatases have been shown to “put the brakes” on IFN signaling. Phosphatases tyrosine-protein phosphatase non-receptor type 6 (SHP1), type 11 (SHP2), and protein phosphatase 2A (PP2A) have all been shown to inhibit JAK-STAT phosphorylation ( 153–155 ), and are all inhibited by zinc ions, predominantly in the nanomolar range ( 156–158 ). Interestingly, PP2A can also inhibit the phosphorylation of IRF3, thus regulating antigen recognition by PRRs ( 159 ).…”

Section: Current Status Of Knowledgementioning

confidence: 99%

The Role of Zinc in Antiviral Immunity

Read

Obeid

Ahlenstiel

et al. 2019

Advances in Nutrition

611

602

View full text Add to dashboard Cite

Zinc is an essential trace element that is crucial for growth, development, and the maintenance of immune function. Its influence reaches all organs and cell types, representing an integral component of approximately 10% of the human proteome, and encompassing hundreds of key enzymes and transcription factors. Zinc deficiency is strikingly common, affecting up to a quarter of the population in developing countries, but also affecting distinct populations in the developed world as a result of lifestyle, age, and disease-mediated factors. Consequently, zinc status is a critical factor that can influence antiviral immunity, particularly as zinc-deficient populations are often most at risk of acquiring viral infections such as HIV or hepatitis C virus. This review summarizes current basic science and clinical evidence examining zinc as a direct antiviral, as well as a stimulant of antiviral immunity. An abundance of evidence has accumulated over the past 50 y to demonstrate the antiviral activity of zinc against a variety of viruses, and via numerous mechanisms. The therapeutic use of zinc for viral infections such as herpes simplex virus and the common cold has stemmed from these findings; however, there remains much to be learned regarding the antiviral mechanisms and clinical benefit of zinc supplementation as a preventative and therapeutic treatment for viral infections.

show abstract

“…Another study has agreeably demonstrated zinc-induced aggregation of Aβ peptides in vitro [ 36 ]. Recently, zinc has also been demonstrated to induce tau hyperphosphorylation by activating the glycogen synthase kinase-3beta (GSK-3β) and inactivating phosphatase like protein phosphatase 2A (PP2A) [ 18 , 35 , 37 ]. However, whether zinc-mediated tau hyperphosphorylation involves the GSK-3β kinase remains controversial as some studies show that the GSK-3β kinase is not activated and only PP2A is inactivated under zinc-induced tau hyperphosphorylation conditions [ 38 ].…”

Section: Essential Biometal Ionsmentioning

confidence: 99%

Metal Ion Effects on Aβ and Tau Aggregation

Kim

Lim

Kim

2018

IJMS

134

153

View full text Add to dashboard Cite

Amyloid and tau aggregation are implicated in manifold neurodegenerative diseases and serve as two signature pathological hallmarks in Alzheimer’s disease (AD). Though aging is considered as a prominent risk factor for AD pathogenesis, substantial evidence suggests that an imbalance of essential biometal ions in the body and exposure to certain metal ions in the environment can potentially induce alterations to AD pathology. Despite their physiological importance in various intracellular processes, biometal ions, when present in excessive or deficient amounts, can serve as a mediating factor for neurotoxicity. Recent studies have also demonstrated the contribution of metal ions found in the environment on mediating AD pathogenesis. In this regard, the neuropathological features associated with biometal ion dyshomeostasis and environmental metal ion exposure have prompted widespread interest by multiple research groups. In this review, we discuss and elaborate on findings from previous studies detailing the possible role of both endogenous and exogenous metal ions specifically on amyloid and tau pathology in AD.

show abstract

Zinc binds to and directly inhibits protein phosphatase 2A in vitro

Cited by 30 publications

References 30 publications

Protein Phosphatase 2A as a Drug Target in the Treatment of Cancer and Alzheimer’s Disease

Protein Phosphatase 2A as a Drug Target in the Treatment of Cancer and Alzheimer’s Disease

The Role of Zinc in Antiviral Immunity

Metal Ion Effects on Aβ and Tau Aggregation

Contact Info

Product

Resources

About