PSEN1/PS1 Cancer Research Results

PSEN1/PS1, Presenilin-1: Click to Expand ⟱
Source:
Type:

PSEN1 - Presenilin-1

Abbreviation: PSEN1, PS1

Type: Intramembrane aspartyl protease / catalytic subunit of the γ-secretase complex

Function: PSEN1 is the principal catalytic component of the γ-secretase complex, which performs intramembrane proteolysis of numerous substrates including amyloid precursor protein (APP) and NOTCH receptors. APP cleavage by PSEN1-containing γ-secretase generates amyloid-β peptides including Aβ40 and Aβ42. PSEN1 also regulates cellular signaling, membrane-protein processing, calcium homeostasis, and neuronal function.

Cancer: ↕ Context-dependent. PSEN1-dependent γ-secretase activity can promote oncogenic signaling through cleavage and activation of NOTCH receptors and other substrates. γ-Secretase inhibition can suppress NOTCH-driven proliferation, survival, stemness, and tumor progression in selected cancers, although PSEN1 function varies substantially according to tumor type and substrate context.

Alzheimer's Disease: ↕ Pathogenic alteration of PSEN1 function is a major cause of autosomal-dominant early-onset Alzheimer's disease. Disease-causing PSEN1 mutations alter γ-secretase processivity and commonly increase the relative production of longer, aggregation-prone Aβ species, particularly the Aβ42/Aβ40 ratio. Many pathogenic mutations reduce overall γ-secretase cleavage efficiency, so Alzheimer's disease is better characterized by abnormal PSEN1 function than by a simple increase or decrease in PSEN1 expression.
Scientific Papers found: Click to Expand⟱
7839- AO,  ISQ,    The Protective Effects of Acer okamotoanum and Isoquercitrin on Obesity and Amyloidosis in a Mouse Model
- in-vivo, AD, NA - in-vivo, Obesity, NA
*Dose↝, For four weeks, 100 and 10 mg/kg/day of EAO and isoquercitrin, respectively, were administered orally
*Obesity↓, Administration of EAO and isoquercitrin significantly decreased body weight in HFD and Aβ-injected mice
*Leptin↓, decrease in leptin and an increase in adiponectin levels compared with the control group
*adiP↑,
*hepatoP↑, EAO- and isoquercitrin-administered groups attenuated liver damage
*PSEN1/PS1↓, administration of EAO and isoquercitrin groups down-regulated amyloidosis-related proteins in the brain such as β-secretase, presenilin (PS)-1 and PS-2 compared with HFD and Aβ-injected mice.
*PSEN2/PS-2↓,
*BACE/β-secretase↓,
*eff↑, EAO and isoquercitrin attenuated HFD and Aβ-induced obesity and amyloidosis, suggesting that they could be effective in preventing and treating both obesity and AD.

7498- H2S,    Hydrogen sulfide down-regulates BACE1 and PS1 via activating PI3K/Akt pathway in the brain of APP/PS1 transgenic mouse
- in-vivo, AD, NA
*BACE/β-secretase↑, After intraperitoneal administration of an H2S donor (NaHS) into APP/PS1 mice, the levels of BACE1, PS1 and pp38MAPK were reduced and ADAM17 increased.
*ADAM17↑,
*PSEN1/PS1↓, H2S inhibits the expression of BACE1 and PS1 by activating PI3K/Akt pathway in AD.
*PI3K↑,
*Akt↑,

7631- Ins,  IP6,    Broad Spectrum Anticancer Activity of Myo-Inositol and Inositol Hexakisphosphate
- Review, Var, NA
other↑, Deregulated inositol metabolism has been recorded in a number of diseases, including cancer, where inositol modulates different critical pathways.
p‑pRB↓, Inositols inhibit pRB phosphorylation, fostering the pRB/E2F complexes formation and blocking progression along the cell cycle.
TumCCA↑,
PI3K↓, Inositols reduce PI3K levels, thus counteracting the activation of the PKC/RAS/ERK pathway downstream of PI3K activation.
Akt↓, Akt activation is severely impaired upon inositol addition
ERK↓, Downregulation of both Akt and ERK leads consequently to NF-kB inhibition and reduced expression of inflammatory markers (COX-2 and PGE2).
NF-kB↓,
COX2/PTGS2↓,
PGE2↓,
PSEN1/PS1↓, Remarkably, inositol-induced downregulation of presenilin-1 interferes with the epithelial-mesenchymal transition and reduces Wnt-activation, β-catenin translocation, Notch-1, N-cadherin, and SNAI1 release.
EMT↓,
Wnt↓,
β-catenin/ZEB1↓,
NOTCH1↓,
N-cadherin↓,
Snail↓,
E-cadherin↑, upregulating Focal Adhesion Kinase and E-cadherin and decreasing Fascin and Cofilin, two main components of pseudopodia, leading hence to invasiveness impairment.
fascin↓,
Cofilin↓,
MMPs↓, inositol-induced inhibition on metalloproteinases and ROCK1/2 release
ROCK1↓,
Dose↝, A mixed western diet provides the human adult with approximately 1 g of total inositol per day. it may be surmised that in western countries low-vegetable consumers may suffer from a relative deficiency of myo-Ins
other↝, InsP6 is often referred to as an antinutrient [20] responsible for iron deficiencies mostly in underdeveloped countries, it should be emphasized that InsP6 displays its antinutritional effects only when the diet is already deprived of trace elements
selectivity↑, specific for cancer cells, given that both InsP6 and myo-Ins did not promote apoptosis in normal cells.
*ROS↓, Myo-Ins counteracts oxidative damage in fish exposed to environmental stresses [114] and significantly inhibits systemic markers of oxidative stress in gynecological patients
*lipid-P↓, thus preventing formation of ADP-iron-oxygen complexes that trigger lipid peroxidation
ROS↑, antioxidant property of inositol is strictly context-dependent as, under specific conditions, both myo-Ins and InsP6 may increase free radical production
NK cell↑, inositol hexakisphosphate and myo-Ins enhance NK activity in mice treated with 1,2-dimethylhydrazine (DMH),
Imm↑, enhancement of immune function
TNF-α↓, InsP6 also modulates the transcription genes for TNF by decreasing it and its receptors in colon cancer cells
ChemoSen↑, inositol hexakisphosphate may potentiate the anticancer effects of conventional chemotherapy in preventing the successful development of cancer implants
Dose↑, Mild side effects (mostly represented by nausea or diarrhea) are reported in a small fraction of subjects, only for doses up to 12 g/day
toxicity↓,
QoL↑, where InsP6 plus myo-Ins treatment is associated with appreciable reduction in tumor burden and improved quality of life
chemoP↑, , if inositols were added along with conventional chemotherapy, colon cancer patients experienced significantly less side effects than controls, as reported in a pilot study
OS↑, Furthermore, prolonged survival and better quality of life have been obtained in some anecdotal cases of breast and lung cancer patients treated with InsP6 and myo-Ins
Dose↝, A study enrolling 26 smokers showed that myo-Ins in a daily dose up to 18 g/p.o. is safe and well tolerated, while inducing a significant regression of individual pulmonary dysplastic lesions
Insulin↓, downregulation of insulin levels, improved glucose utilization through the oxidative cycle, and inhibition of lipogenesis).
glucose↝,
lipoGen↓,
eff↑, There is a widespread consensus suggesting that InsP6 and myo-Ins act synergistically when added in association.


Showing Research Papers: 1 to 3 of 3

* indicates research on normal cells as opposed to diseased cells
Total Research Paper Matches: 3

Pathway results for Effect on Cancer / Diseased Cells:


NA, unassigned(tgid=0) ⓘ

PSEN1/PS1↓, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

ROS↑, 1,  

Mitochondria & Bioenergetics(tgid=3) ⓘ

Insulin↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

glucose↝, 1,   lipoGen↓, 1,  

Cell Death(tgid=5) ⓘ

Akt↓, 1,  

Transcription & Epigenetics(tgid=7) ⓘ

other↑, 1,   other↝, 1,   p‑pRB↓, 1,  

Cell Cycle & Senescence(tgid=11) ⓘ

TumCCA↑, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

EMT↓, 1,   ERK↓, 1,   NOTCH1↓, 1,   PI3K↓, 1,   Wnt↓, 1,  

Migration(tgid=13) ⓘ

Cofilin↓, 1,   E-cadherin↑, 1,   fascin↓, 1,   MMPs↓, 1,   N-cadherin↓, 1,   ROCK1↓, 1,   Snail↓, 1,   β-catenin/ZEB1↓, 1,  

Immune & Inflammatory Signaling(tgid=16) ⓘ

COX2/PTGS2↓, 1,   Imm↑, 1,   NF-kB↓, 1,   NK cell↑, 1,   PGE2↓, 1,   TNF-α↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

ChemoSen↑, 1,   Dose↑, 1,   Dose↝, 2,   eff↑, 1,   selectivity↑, 1,  

Functional Outcomes(tgid=23) ⓘ

chemoP↑, 1,   OS↑, 1,   QoL↑, 1,   toxicity↓, 1,  
Total Targets: 38

Pathway results for Effect on Normal Cells:


NA, unassigned(tgid=0) ⓘ

PSEN1/PS1↓, 2,   PSEN2/PS-2↓, 1,  

Redox & Oxidative Stress(tgid=1) ⓘ

lipid-P↓, 1,   ROS↓, 1,  

Core Metabolism/Glycolysis(tgid=4) ⓘ

adiP↑, 1,  

Cell Death(tgid=5) ⓘ

Akt↑, 1,  

Proliferation, Differentiation & Cell State(tgid=12) ⓘ

PI3K↑, 1,  

Cellular Microenvironment(tgid=17) ⓘ

ADAM17↑, 1,  

Protein Aggregation(tgid=19) ⓘ

BACE/β-secretase↓, 1,   BACE/β-secretase↑, 1,  

Hormonal & Nuclear Receptors(tgid=20) ⓘ

Leptin↓, 1,  

Drug Metabolism & Resistance(tgid=21) ⓘ

Dose↝, 1,   eff↑, 1,  

Functional Outcomes(tgid=23) ⓘ

hepatoP↑, 1,   Obesity↓, 1,  
Total Targets: 15

Scientific Paper Hit Count for: PSEN1/PS1, Presenilin-1
1 Acer okamotoanum
1 isoquercitrin
1 hydrogen sulfide
1 Inositol
1 IP6 (Inositol 1,2,3,4,5,6-hexakisphosphate)
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

Filter Conditions: Pro/AntiFlg:%  IllCat:%  CanType:%  Cells:%  prod#:%  Target#:1650  State#:%  Dir#:1
  wNotes=on  sortOrder:rid,rpid

 

Home Page