PP2A Cancer Research Results

PP2A, serine/threonine phosphatase: Click to Expand ⟱
Source:
Type:
Protein Phosphatase 2A (PP2A) plays a critical role in Alzheimer’s disease (AD), especially in relation to tau pathology.
-PP2A dephosphorylates tau, thus reducing its toxicity.
-MID1 Negatively Regulates PP2A
-In AD, PP2A activity is decreased, leading to accumulation of hyperphosphorylated tau.
-Amyloid-β (Aβ) peptides may inhibit PP2A, indirectly promoting tau pathology.
-Aβ and tau pathologies are interconnected, and PP2A sits at a crossroads of both.

Some natural products that might upregulate PP2A:
-resveratrol
-Sodium selenate
-Berberine
-Fisetin
-Metformin (via indirect mechanisms)
Scientific Papers found: Click to Expand⟱
4298- BBR,    Berberine mitigates cognitive decline in an Alzheimer’s Disease Mouse Model by targeting both tau hyperphosphorylation and autophagic clearance
- in-vivo, AD, NA
*cognitive↑, Berberine could improve 3×Tg AD mice’s cognitive function
*p‑tau↓, Berberine could attenuate the hyperphosphorylation of tau
*GSK‐3β↓, attenuated the hyperphosphorylation of tau. via modulating the activity of Akt/glycogen synthase kinase-3β and protein phosphatase 2A
*PP2A↑, inhibition of GSK3β or activation of PP2A attenuates tau hyperphosphorylation, thus, ameliorates cognitive impairment
*memory↑, Berberine-treated mice showed better performance in spatial learning and memory test
*Akt↑, Berberine decreases tau phosphorylation via activation of Akt and inhibition of GSK3β
*LC3II↑, both LC3-Ⅱ and Beclin-1 in the hippocampus of BBR-treated group were dramatically increased compared with the 3×Tg AD mice
*Beclin-1↑,

4302- Gins,    Panax ginseng: A modulator of amyloid, tau pathology, and cognitive function in Alzheimer's disease
- Review, AD, NA
*neuroP↑, highlighting neuroprotective mechanisms, such as the inhibition of Aβ production, enhanced Aβ clearance, and suppression of tau hyperphosphorylation.
*Aβ↓,
*p‑tau↓,
*cognitive↑, Research on P. ginseng and its bioactive ginsenosides has shown potential for improving cognitive function in AD models
*eff↑, particularly pronounced effects in individuals lacking apolipoprotein ε4 allele.
*PKA↑, Upregulates the PKA/CREB signaling pathway
*CREB↑,
*BACE↓, Inhibits BACE1 activity
*ADAM10↑, Enhances the expression of ADAM10 and reduces BACE1 expression through the activation of MAPK/ERK and PI3K/AKT
*MAPK↑,
*ERK↑,
*PI3K↑,
*Akt↑,
*NRF2↑, Activates the Nrf2/Keap1 signaling pathway
*PPARγ↓, Inhibits PPARγ phosphorylation and upregulates the expression of IDE
*IDE↑,
*APP↓, downregulates the expression of BACE1 and APP
*PP2A↑, Ginsenoside Rb1 enhances PP2A levels, thereby facilitating tau dephosphorylation and reducing p-tau levels observed in animal studies
*memory↑, The 400 mg dose of ginseng extract significantly improved “Quality of Memory” and “Secondary Memory” at all post-dose time points,

5254- NCL,    The magic bullet: Niclosamide
- Review, Var, NA
Wnt↓, In particular, niclosamide inhibits multiple oncogenic pathways such as Wnt/β-catenin, Ras, Stat3, Notch, E2F-Myc, NF-κB, and mTOR and activates tumor suppressor signaling pathways such as p53, PP2A, and AMPK.
β-catenin/ZEB1↓,
RAS↓,
STAT3↓,
NOTCH↓,
E2Fs↓,
mTOR↓,
eff↑, Moreover, niclosamide potentially improves immunotherapy by modulating pathways such as PD-1/PDL-1.
PD-1↓,
PD-L1↓, primarily through PD-L1 ligand downregulation in cancer cells.
BioAv↝, The original pharmacokinetics study showed that the maximal serum concentration can reach 0.25-6.0ug/ml (0.76-18.34 µM) following administration of a single 2g dose (11).
toxicity↓, a strong safety profile and tolerability in humans.
BioAv↑, A potential solution to the aforementioned challenge is niclosamide ethanolamine (NEN), a salt form of niclosamide that also functions as a mitochondrial uncoupler with a superior safety profile and enhanced bioavailability
ETC↑, NEN activates the ETC to boost NADH oxidation, thereby leading to an increased intracellular NAD+/NADH ratio and driving the TCA cycle forward.
NADH:NAD↓,
TCA↑,
Warburg↓, leading to a reversal of the Warburg effect and the induction of cellular differentiation
Diff↑,
AMPK↑, figure 3
P53↑,
PP2A↑,
HIF-1↓,
KRAS↓,
Myc↓,
RadioS↑, leading to a reversal of the Warburg effect and the induction of cellular differentiation
ChemoSen↑, Niclosamide has shown synergistic anti-tumor effects with a broad spectrum of chemotherapy drugs.
Dose↝, In this trial, either 500mg or 1000mg niclosamide was given three times daily to patients. However, the maximal plasma concentration ranged from 35.7–82 ng/mL (0.1µM-0.25 µM), a range that failed to be consistently above the minimum effective concent
Dose↑, In contrast, the ongoing clinical trial NCT02807805 is administering 1200 mg of reformulated orally bioavailable niclosamide orally (PO) three times daily to patients, resulting in 0.21µM-0.723 plasma niclosamide concentrations exceeding the therape

4289- RES,    Resveratrol Attenuates Formaldehyde Induced Hyperphosphorylation of Tau Protein and Cytotoxicity in N2a Cells
- in-vitro, AD, NA
*antiOx↑, Resveratrol (Res), as a polyphenol anti-oxidant, has been considered to have therapeutic potential for the treatment of AD.
*p‑tau↓, Res significantly decreased FA-induced cytotoxicity, reduced cell apoptosis rates, and inhibited the hyperphosphorylation of tau protein at Thr181 in a dose-dependent manner.
*GSK‐3β↓, Further tests revealed that this effect was associated with the suppression of glycogen synthase kinase (GSK-3β)
*CaMKII ↓, and calmodulin-dependent protein kinase II (CaMKII) activities, both of which are important kinases for tau protein hyperphosphorylation.
*PP2A↑, Res was found to increase the activity of phosphoseryl/phosphothreonyl protein phosphatase-2A (PP2A).
*neuroP↑, Neuroprotective effects of Res against FA-induced cytotoxicity

4288- RES,    Trans-resveratrol Inhibits Tau Phosphorylation in the Brains of Control and Cadmium Chloride-Treated Rats by Activating PP2A and PI3K/Akt Induced-Inhibition of GSK3β
- in-vivo, AD, NA
*memory↑, RES improved both short and long-term memory as analyzed by novel object recognition task and significantly increased brain levels of glutathione in both control and CdCl2-treated rats.
*GSH↑,
*ROS↓, It also inhibited ROS levels of malondialdehyde in the brains of CdCl2-treated rats.
*MDA↓,
*p‑tau↓, RES decreased the phosphorylation rate of Tau at Ser199 and Ser296.
*PI3K↑, RES activated PI3K/Akt signaling pathway in both control and CdCl2 treated rats by increasing levels of p-PI3K (Tyr607) and p-Akt (Ser473)
*Akt↑,
*AMPK↑, significant increase in the levels of AMPK and p-AMPK, known upstream regulators of PI3K/Akt signaling pathway.
*PP2A↑, RES inhibits Tau phosphorylation in rat’s brain by activating PP2A protein and AMPK/PI3K/Akt-induced inhibition of GSK3β.
*GSK‐3β↓,

4286- RES,    Neuroprotective Properties of Resveratrol and Its Derivatives—Influence on Potential Mechanisms Leading to the Development of Alzheimer’s Disease
- Review, AD, NA
*neuroP↑, state of the art evidence on the role of resveratrol (RSV) in neuroprotection is presented
*Inflam↓, Resveratrol (3,5,4′-trihydroxy-trans-stilbene), a polyphenol contained in red wine, peanuts, and some berries, is known for its anti-atherosclerotic, anti-inflammatory, antioxidant, and longevity-promoting properties
*antiOx↑,
*GSH↑, ↑glutathione in brain
*HO-1↑, ↑HO-1 ↓iNOS in hippocampus
*iNOS↓,
*BDNF↑, ↑BDNF, ↑pCREB, ↑PKA, ↑BCl-2 expression, ↓BAX expression, ↓IL-1β, IL-6, in hippocampus
*p‑CREB↑,
*PKA↑,
*Bcl-2↑,
*BAX↓,
*IL1β↓,
*IL6↓,
*MMP9↓, ↓MMP-9 in cerebrospinal fluid
*memory↑, ↑memory performance
*AMPK↑, ↑AMPK, ↑PGC-1, ↓NF-κB / IL-1β / NLRP3 in hippocampus and prefrontal cortex
*PGC-1α↓,
*NF-kB↓,
*Aβ↓, may counteract the formation of neurotoxic Aβ
*SIRT1↑, Resveratrol via SIRT-1 can, therefore, be expected to reduce the level of hyperphosphorylated tau and provide protection against neurodegeneration.
*p‑tau↓,
*PP2A↑, resveratrol by lowering the expression of MID1 ubiquitin ligase increases protein phosphatase 2A (PP2A) activity and promotes tau dephosphorylation by preventing its accumulation
*lipid-P↓, resveratrol abolishes Aβ-induced lipid peroxidation and expression of heme oxygenase-1 (HO-1) reduction;
*NLRP3↓, Researchers achieved a significant reduction in the levels of NF-κB (nuclear factor κ-light-chain enhancer of activated B cell), interleukin 1β and NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammation markers
*BACE↓, figure 1

4284- RES,    Resveratrol induces dephosphorylation of Tau by interfering with the MID1-PP2A complex
- in-vitro, AD, HEK293 - NA, Stroke, NA - in-vivo, AD, NA
*p‑tau↓, Resveratrol induces dephosphorylation of Tau
*PP2A↑, resveratrol, a polyphenol, significantly induces PP2A activity and reduces Tau phosphorylation at PP2A-dependent epitopes.
*neuroP↑, resveratrol is more and more being established as a neuroprotective drug after ischemic brain injury and in neurodegenerative disorders including Parkinson’s Disease13,14, AD15,16 and Huntington’s Disease
*antiOx↑, resveratrol has anti-oxidant activity19,20, inhibits cycloxygenase activity21,22, ribonucleotide reductase23, protein kinase C24, DNA polymerase 25 and has antiestrogenic properties26,27 and anti-platelet activity
COX2↓,
*AntiAg↑,
*SIRT1↑, it activates Sirt1, an NAD+-dependent protein deacetylase28,29 and also has been demonstrated to activate AMP kinase (AMPK)30,31, an important glucose sensor that inhibits acetyl-CoA carboxylase, thereby increasing oxidation of fatty acids and decre
*AMPK↑,
*Acetyl-CoA↓,
*FAO↑,
*ADAM10↑, Resveratrol has been suggested to induce the α-secretase ADAM10, which outcompetes BACE1 and thereby reduces Aβ-production
*BACE↓,
*Aβ↓,
*memory↑, interestingly, the resveratrol-mediated reduction of Aβ increases life span and improves learning and memory
*Inflam↓, reduces neuroinflammation47 and reduces oxidative stress48.
*ROS↓,


Showing Research Papers: 1 to 7 of 7

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 7

Pathway results for Effect on Cancer / Diseased Cells:


Mitochondria & Bioenergetics ⓘ

ETC↑, 1,  

Core Metabolism/Glycolysis ⓘ

AMPK↑, 1,   NADH:NAD↓, 1,   TCA↑, 1,   Warburg↓, 1,  

Cell Death ⓘ

Myc↓, 1,  

DNA Damage & Repair ⓘ

P53↑, 1,  

Cell Cycle & Senescence ⓘ

E2Fs↓, 1,  

Proliferation, Differentiation & Cell State ⓘ

Diff↑, 1,   mTOR↓, 1,   NOTCH↓, 1,   RAS↓, 1,   STAT3↓, 1,   Wnt↓, 1,  

Migration ⓘ

KRAS↓, 1,   β-catenin/ZEB1↓, 1,  

Angiogenesis & Vasculature ⓘ

HIF-1↓, 1,  

Immune & Inflammatory Signaling ⓘ

COX2↓, 1,   PD-1↓, 1,   PD-L1↓, 1,  

Protein Aggregation ⓘ

PP2A↑, 1,  

Drug Metabolism & Resistance ⓘ

BioAv↑, 1,   BioAv↝, 1,   ChemoSen↑, 1,   Dose↑, 1,   Dose↝, 1,   eff↑, 1,   RadioS↑, 1,  

Clinical Biomarkers ⓘ

KRAS↓, 1,   Myc↓, 1,   PD-L1↓, 1,  

Functional Outcomes ⓘ

toxicity↓, 1,  
Total Targets: 32

Pathway results for Effect on Normal Cells:


Redox & Oxidative Stress ⓘ

antiOx↑, 3,   GSH↑, 2,   HO-1↑, 1,   lipid-P↓, 1,   MDA↓, 1,   NRF2↑, 1,   ROS↓, 2,  

Mitochondria & Bioenergetics ⓘ

PGC-1α↓, 1,  

Core Metabolism/Glycolysis ⓘ

Acetyl-CoA↓, 1,   AMPK↑, 3,   CREB↑, 1,   p‑CREB↑, 1,   FAO↑, 1,   PPARγ↓, 1,   SIRT1↑, 2,  

Cell Death ⓘ

Akt↑, 3,   BAX↓, 1,   Bcl-2↑, 1,   iNOS↓, 1,   MAPK↑, 1,  

Kinase & Signal Transduction ⓘ

CaMKII ↓, 1,  

Autophagy & Lysosomes ⓘ

Beclin-1↑, 1,   LC3II↑, 1,  

Proliferation, Differentiation & Cell State ⓘ

ERK↑, 1,   GSK‐3β↓, 3,   PI3K↑, 2,  

Migration ⓘ

AntiAg↑, 1,   APP↓, 1,   MMP9↓, 1,   PKA↑, 2,  

Immune & Inflammatory Signaling ⓘ

IL1β↓, 1,   IL6↓, 1,   Inflam↓, 2,   NF-kB↓, 1,  

Synaptic & Neurotransmission ⓘ

ADAM10↑, 2,   BDNF↑, 1,   p‑tau↓, 6,  

Protein Aggregation ⓘ

Aβ↓, 3,   BACE↓, 3,   IDE↑, 1,   NLRP3↓, 1,   PP2A↑, 6,  

Drug Metabolism & Resistance ⓘ

eff↑, 1,  

Clinical Biomarkers ⓘ

IL6↓, 1,  

Functional Outcomes ⓘ

cognitive↑, 2,   memory↑, 5,   neuroP↑, 4,  
Total Targets: 47

Scientific Paper Hit Count for: PP2A, serine/threonine phosphatase
4 Resveratrol
1 Berberine
1 Ginseng
1 Niclosamide (Niclocide)
Query results interpretion may depend on "conditions" listed in the research papers.
Such Conditions may include : 
  -low or high Dose
  -format for product, such as nano of lipid formations
  -different cell line effects
  -synergies with other products 
  -if effect was for normal or cancerous cells

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