Restoration of PP2A levels in inflamed microglial cells: Important for neuroprotective M2 microglial viability

Nematullah,; Hoda, M. N.; Nimker, Shwetanjali; Khan, Farah

doi:10.1016/j.taap.2020.115294

Cited by 4 publications

(2 citation statements)

References 37 publications

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“… 147 , 148 PP2A also had an effect on the transformation of the M1/M2 microglial population and influenced neuroinflammation and neuronal functions. 149 …”

Section: The Signaling Pathways Regulated By the Protein Phosphatases...mentioning

confidence: 99%

Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy

Pan

Zhou

Zhang

et al. 2022

Sig Transduct Target Ther

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Inflammation is the common pathological basis of autoimmune diseases, metabolic diseases, malignant tumors, and other major chronic diseases. Inflammation plays an important role in tissue homeostasis. On one hand, inflammation can sense changes in the tissue environment, induce imbalance of tissue homeostasis, and cause tissue damage. On the other hand, inflammation can also initiate tissue damage repair and maintain normal tissue function by resolving injury and restoring homeostasis. These opposing functions emphasize the significance of accurate regulation of inflammatory homeostasis to ameliorate inflammation-related diseases. Potential mechanisms involve protein phosphorylation modifications by kinases and phosphatases, which have a crucial role in inflammatory homeostasis. The mechanisms by which many kinases resolve inflammation have been well reviewed, whereas a systematic summary of the functions of protein phosphatases in regulating inflammatory homeostasis is lacking. The molecular knowledge of protein phosphatases, and especially the unique biochemical traits of each family member, will be of critical importance for developing drugs that target phosphatases. Here, we provide a comprehensive summary of the structure, the “double-edged sword” function, and the extensive signaling pathways of all protein phosphatases in inflammation-related diseases, as well as their potential inhibitors or activators that can be used in therapeutic interventions in preclinical or clinical trials. We provide an integrated perspective on the current understanding of all the protein phosphatases associated with inflammation-related diseases, with the aim of facilitating the development of drugs that target protein phosphatases for the treatment of inflammation-related diseases.

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“… 147 , 148 PP2A also had an effect on the transformation of the M1/M2 microglial population and influenced neuroinflammation and neuronal functions. 149 …”

Section: The Signaling Pathways Regulated By the Protein Phosphatases...mentioning

confidence: 99%

Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy

Pan

Zhou

Zhang

et al. 2022

Sig Transduct Target Ther

View full text Add to dashboard Cite

show abstract

“…Furthermore, PP2A dephosphorylates amyloid β (Aβ) precursor protein (APP) at Thr668 [32], thus hindering the APP proteolytic processing and Aβ synthesis [33]. Finally, PP2A dephosphorylates several kinases controlling inflammatory or stress signaling pathways to dissipate inflammation [34,35] and promote the viability of neuroprotective M2 microglia [36], or p47phox, whose dephosphorylation inactivates the whole NADPH oxidase complex to reduce oxidative stress [37]. Another stress kinase is MAP3K dual leucine zipper (DLK), overexpressed in AD brains [38], which is inhibited by PP2A in neurons [39].…”

Section: Introductionmentioning

confidence: 99%

C-glycosides analogues of the okadaic acid central fragment exert neuroprotection via restoration of PP2A-phosphatase activity: A rational design of potential drugs for Alzheimer's disease targeting tauopathies

Arribas

Viejo

Bravo

et al. 2023

European Journal of Medicinal Chemistry

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Protein Phosphatase 2A Regulates Phenotypic and Metabolic Alteration of Microglia Cells in HFD-Associated Vascular Dementia Mice via TNF-α/Arg-1 Axis

et al. 2023

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Restoration of PP2A levels in inflamed microglial cells: Important for neuroprotective M2 microglial viability

Cited by 4 publications

References 37 publications

Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy

Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy

C-glycosides analogues of the okadaic acid central fragment exert neuroprotection via restoration of PP2A-phosphatase activity: A rational design of potential drugs for Alzheimer's disease targeting tauopathies

Protein Phosphatase 2A Regulates Phenotypic and Metabolic Alteration of Microglia Cells in HFD-Associated Vascular Dementia Mice via TNF-α/Arg-1 Axis

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