MUDr. Dana Maňasková


Vyhledávání na medicinman.cz
 

Teoretické podpůrné tipy

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  • Please find some natural chemical stuff or combination of compounds, that can stimulate most of the haploinsufficient genes and their proteins
  • I can suggest some general considerations and substances that have been studied for their potential effects on gene expression or related cellular processes.
    • Effects may be nuanced
    • Interventions with caution, considering individual health, existing medical conditions, and potential interactions with medications.

Resveratrol

  • Found in red wine, grapes, and certain berries, resveratrol has been studied for its potential antioxidant and anti-inflammatory effects. It may have some impact on gene expression related to aging and cellular function.

Curcumin

  • A component of turmeric, curcumin has been investigated for its anti-inflammatory and antioxidant properties. It may modulate gene expression related to inflammation and cellular stress.

Green Tea Extract

  • Epigallocatechin gallate (EGCG), found in green tea, has been studied for its potential effects on various cellular processes, including apoptosis and inflammation. It may impact gene expression related to these processes.

Quercetin

  • Present in foods like apples, onions, and berries, quercetin has antioxidant properties and has been studied for potential anti-inflammatory effects. It may influence gene expression related to inflammation.

Omega-3 Fatty Acids

  • Found in fatty fish and flaxseeds, omega-3 fatty acids may have anti-inflammatory effects and could potentially influence gene expression related to inflammation and lipid metabolism.

Sulforaphane

  • Present in cruciferous vegetables like broccoli, sulforaphane has been studied for its potential anti-cancer and anti-inflammatory effects. It may impact gene expression related to these processes.

Catechins

  • Found in tea, particularly green tea, catechins may have antioxidant and anti-inflammatory effects, potentially influencing gene expression related to these processes.

Genistein

  • Found in soy products, genistein is a phytoestrogen that has been studied for its potential effects on gene expression, particularly in relation to hormonal pathways.
Chat GPT, 2023/11/27

Apigenin

  • Found in parsley, celery, and chamomile tea, apigenin is a flavonoid with antioxidant and anti-inflammatory properties. It has been studied for its potential influence on gene expression related to inflammation and cancer.

Ellagic Acid

  • Found in berries, nuts, and pomegranates, ellagic acid has antioxidant properties and may impact gene expression related to cell cycle regulation and apoptosis.

Allicin

  • Present in garlic, allicin has been studied for its potential antimicrobial and anti-inflammatory effects. It may influence gene expression related to immune function and inflammation.

Gingerol

  • Found in ginger, gingerol has anti-inflammatory and antioxidant properties. It has been studied for its potential effects on gene expression related to inflammation and oxidative stress.

Lycopene

  • Found in tomatoes, watermelon, and pink grapefruit, lycopene is a carotenoid with antioxidant properties. It has been investigated for its potential impact on gene expression related to cancer.

Berberine

  • Found in several plants, including goldenseal and barberry, berberine has been studied for its potential effects on gene expression related to metabolism and inflammation.

Curcuminoids

  • Besides curcumin, turmeric contains other curcuminoids that may have similar anti-inflammatory and antioxidant effects.

Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA)

  • Omega-3 fatty acids found in fatty fish, algae, and fish oil supplements have anti-inflammatory properties and may influence gene expression related to inflammation and lipid metabolism.

Chlorogenic Acid

  • Found in coffee, fruits, and vegetables, chlorogenic acid has antioxidant properties and has been studied for its potential effects on gene expression related to inflammation and metabolism.

Quinones

  • Certain compounds like coenzyme Q10 (ubiquinone) found in meat and fish, and vitamin K2 (menaquinone) found in fermented foods, have been studied for their potential effects on gene expression related to energy metabolism and cellular processes.

Binding of Shh to its receptor - Patched 1 (Ptch1) or Ptch2

  • Relieves inhibition of the G-protein coupled receptor Smoothened (Smo)
  • Activated Smo inhibits proteolytic processing of the GLI transcriptional effectors Gli2 or Gli3 into truncated repressor
    • Forms through destabilization of complexes between Gli2 or Gli3 and Suppressor of Fused (Sufu).
  • The resulting accumulation of full-length GLI proteins in the nucleus
    • Promotes the expression of Hh target genes
  • bmcresnotes.biomedcentral.com/articles/10.1186/s13104-021-05714-5

Inhibice Ptch1, Ptch2, and Hhip

Shh metabolická dráha - stimulace

  • Alobar HPE to microcephaly and hypoplasia of the pituitary gland
  • HPE to an asymptomatic form in another family
  • Genetic heterogeneity of HPE
    • SHH mutations are associated with a broad spectrum of cerebral midline defects
  • academic.oup.com/hmg/article/8/9/1683/815654

Purmorphamine and SAG (Smoothened Agonist)

  • Are known to activate the Sonic Hedgehog pathway
  • These compounds can act as agonists to stimulate the pathway.
Chen, J.K., Taipale, J., Cooper, M.K., and Beachy, P.A. (2002). Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened. Genes Dev. 16, 2743–2748.
Sasaki, H., Nishizaki, Y., Hui, C., Nakafuku, M., and Kondoh, H. (1999). Regulation of Gli2 and Gli3 activities by an amino-terminal repression domain: implication of Gli2 and Gli3 as primary mediators of Shh signaling. Development 126, 3915–3924.

Activation of the Smoothened (Smo) receptor

  • Is a critical step in the Sonic Hedgehog (Shh) signaling pathway

Sonic Hedgehog (Shh) Ligand

  • Leading to Smo activation.

Purmorphamine and Smoothened Agonist (SAG)

  • Syntetic

Lipids, particularly cholesterol

  • Play a role in Smo activation
  • Changes in cholesterol levels can impact the conformation and activity of Smo.

Cyclopamine

  • Often described as an inhibitor of the Hh pathway, cyclopamine can have dual effects.
  • At lower concentrations, it inhibits Smo,
  • At higher concentrations, it can activate Smo.

cAMP (cyclic adenosine monophosphate) levels

  • Can modulate Smo activity through a complex interplay with other signaling pathways.

Dynamin

  • Process of endocytosis, particularly mediated by dynamin
  • Implicated in Smo activation.
  • Internalization and trafficking of Smo within the cell can impact its signaling activity.

Kinases can phosphorylate and regulate Smo.

Casein kinase 1 (CK1) and glycogen synthase kinase 3 (GSK3)

  • Phosphorylate Smo, affecting its stability and activity.

Protein Kinase A (PKA)

  • Can influence the Shh pathway.
  • In the absence of Shh, PKA phosphorylates Smo, leading to its inhibition.
    • Shh signaling relieves this inhibition.

Beta-Arrestins

  • Involved in GPCR signaling, have been shown to interact with Smo and influence its activity.
  • This interaction can impact Smo localization and function.

Protein Phosphatase 2 (PP2A)

  • Dephosphorylate Smo, influencing its activation state.
  • Phosphorylation is a key regulatory mechanism for Smo activity.

Adenosine Deaminase (ADA)

  • Purine metabolism
  • Modulate Shh signaling by affecting the cAMP-PKA pathway and subsequently influencing Smo activity.

AMP-Activated Protein Kinase (AMPK)

  • Cellular energy sensor, has been suggested to regulate Shh signaling by modulating the activity of Smo.

Protein Kinase CK2

  • Kinase that can phosphorylate Smo, and its activity
  • Associated with the regulation of Smo function in the context of Shh signaling.

Oxysterols - cholesterol

  • Stimulate Sonic hedgehog signal transduction and proliferation
  • Holoprosencephaly-like malformations, Smith–Lemli–Opitz syndrome and desmosterolosis
    • Result from defects in the 7-dehydrocholesterol reductase and 3b-hydroxysterol-d24-reductase enzymes

25-OHC and 20-OHC

  • Can activate ptc1-lacZ expression with the same maximal efficacy as the known Smo-binding agonist, SAG.

Impairment of sterol synthesis

  • Has previously been shown to block Shh signal transduction.

Certain sterols

  • Hypotetický závěr - krmit vaječné žloutky, nedávat statiny, nadbytek AA vyvážit rybím tukem
  • Prevence deficitu vitamínu D


Stimulace signalizace Shh genu a následně proteinu na zbylém nepoškozeném raménku chrom. 7

Curcumin

  • Curcumin, the active compound in turmeric, has been suggested to modulate the Sonic Hedgehog pathway

Resveratrol

  • Found in red wine and grapes, resveratrol has been investigated for its potential role in activating Sonic Hedgehog signaling

Epigallocatechin-3-gallate (EGCG)

  • Present in green tea, EGCG has shown some effects on Sonic Hedgehog pathway regulation

Cyclopamine

  • While not a natural compound, cyclopamine is a steroidal alkaloid derived from plants like Veratrum californicum. It has been studied for its inhibitory effects on the Sonic Hedgehog pathway

Guggulsterone

  • Extracted from the Commiphora wightii plant, guggulsterone has been investigated for its potential to modulate Sonic Hedgehog signaling

Berberine

  • Found in various plants, including Berberis vulgaris, berberine has been investigated for its role in modulating Sonic Hedgehog pathway activity

Quercetin

  • A flavonoid present in fruits and vegetables, quercetin has shown some promise in influencing Sonic Hedgehog signaling

Salidroside

  • Extracted from Rhodiola rosea, salidroside has been studied for its potential impact on the Sonic Hedgehog pathway

Fisetin

  • Found in strawberries and other fruits, fisetin has been explored for its potential to modulate Sonic Hedgehog signaling

Honokiol

  • Derived from the bark of Magnolia trees, honokiol has been suggested to influence Sonic Hedgehog signaling in certain studies

Betulinic Acid

  • Found in the bark of certain trees, betulinic acid has been investigated for its role in modulating the Sonic Hedgehog pathway

Luteolin

  • Present in various fruits and vegetables, luteolin has been studied for its potential impact on Sonic Hedgehog signaling

Allicin

  • A compound found in garlic, allicin has been suggested to affect Sonic Hedgehog signaling in some studies

Genistein

  • Found in soy products, genistein has been explored for its potential to influence Sonic Hedgehog pathway activity

Baicalein

  • Derived from Scutellaria baicalensis, baicalein has been studied for its potential effects on Sonic Hedgehog signaling

Ellagic Acid

  • Found in various fruits, ellagic acid has been investigated for its role in modulating Sonic Hedgehog pathway activity

Naringenin

  • Present in citrus fruits, naringenin has been studied for its potential impact on Sonic Hedgehog signaling

Astragaloside IV

  • Derived from the herb Astragalus membranaceus, astragaloside IV has been suggested to influence Sonic Hedgehog signaling in certain studies

Silymarin

  • Found in milk thistle, silymarin has been explored for its potential to modulate Sonic Hedgehog pathway activity

Piperine

  • Obtained from black pepper, piperine has been investigated for its potential effects on Sonic Hedgehog signaling

Salvianolic Acid B

  • Found in Salvia miltiorrhiza (Danshen), salvianolic acid B has been studied for its potential modulation of Sonic Hedgehog signaling

Oleanolic Acid

  • Present in various plants, including olive oil, oleanolic acid has been investigated for its role in Sonic Hedgehog pathway regulation

Forskolin

  • Derived from the Indian Coleus plant, forskolin has been suggested to affect Sonic Hedgehog signaling in certain studies

Betaine

  • Found in beets and other foods, betaine has been explored for its potential impact on Sonic Hedgehog pathway activity

Hesperidin

  • Present in citrus fruits, hesperidin has been studied for its potential effects on Sonic Hedgehog signaling

Purmorphamine

  • This small molecule has been studied for its ability to activate the Sonic Hedgehog pathway and has been used in laboratory research

SAG (Smoothened Agonist)

  • SAG is a synthetic small molecule that activates the Smoothened receptor, a component of the Sonic Hedgehog pathway

Shh-Np (Sonic Hedgehog-N Terminus Peptide)

  • This is a peptide derived from the N-terminus of Sonic Hedgehog protein, and it has been studied for its potential stimulatory effects on the pathway

Arsenic Trioxide (ATO)

  • Arsenic trioxide has been investigated for its potential role in activating the Sonic Hedgehog pathway, particularly in the context of certain cancers

Purvalanol A

  • This compound, which is a cyclin-dependent kinase inhibitor, has been studied for its effects on the Sonic Hedgehog pathway and cell cycle regulation

SANT-1

  • SANT-1 is a small molecule that has been used as an inhibitor of the Sonic Hedgehog pathway. It's worth noting that while it inhibits the pathway in some contexts, its effects may vary

Activation of Smoothened (Smo) Receptor

  • Smoothened is a transmembrane protein that plays a key role in transducing the Shh signal. Small molecules that activate Smoothened, such as Smoothened agonists (e.g., SAG), can enhance Shh signaling.

Inhibition of Ptch1 (Patched-1) Receptor

Ptch1

  • Normally inhibits Smoothened in the absence of Shh ligand binding. Inhibiting Ptch1 can lead to the activation of Smoothened and downstream Shh signaling.

Stabilizing Gli proteins

  • Can enhance their transcriptional activity and promote Shh signaling.

Targeting downstream effectors of Shh signaling

  • Genes involved in cell cycle regulation and differentiation,
    • Can also influence the overall impact of Shh on neurodevelopment.

Modulation of Crosstalk with Other Signaling Pathways

  • Shh signaling often interacts with other signaling pathways during neurodevelopment.

Promotion of Shh-Responsive Cell Types

  • May involve promoting the differentiation of specific neural cell populations.

Purmorphamine

  • Small molecule has been studied in preclinical models for its ability to activate the Sonic Hedgehog pathway

Physical Exercise

  • Suggested to influence Shh signaling, particularly in the context of neurogenesis.
  • Exercise-induced activation of Shh signaling has been observed in studies involving the central nervous system

Vitamin A and Retinoic Acid

  • Retinoic acid, derived from vitamin A, has been implicated in the regulation of Shh signaling during embryonic development

Vitamin D

  • Vitamin D has been associated with the modulation of Shh signaling in certain cellular contexts.
  • Vignatol lze kapat do nosu - nedráždí a proniká odtud do mozku, kde působí jako růstový faktor pro neurony

Mechanical forces

  • Shear stress, have been shown to influence Shh signaling in various tissues.

MicroRNAs (miRNAs)

  • Some identified as regulators of Shh signaling
  • Can either enhance or inhibit Shh signaling by targeting different components of the pathway

Inflammation

  • Can affect Shh signaling
  • Certain cytokines and inflammatory mediators have been implicated in modulating Shh pathway activity

Hypoxia

  • Low oxygen levels (hypoxia) can influence Shh signaling, particularly in the context of tissue development and repair

Estrogen

  • Has been reported to modulate Shh signaling in certain tissues, including the reproductive system

Glutamate

  • Major excitatory neurotransmitter, has been implicated in Shh signaling in the context of neural development

Hedgehog-Interacting Protein (HHIP)

  • protein that can bind to Sonic Hedgehog and regulate its activity.
  • Modulating HHIP levels has been suggested as a potential way to influence Shh signaling

Heparan Sulfate Proteoglycans (HSPGs)

  • HSPGs, which are components of the extracellular matrix, play a role in the regulation of Shh signaling by interacting with Shh ligands

Sulfatases

  • Enzymes involved in the modification of extracellular matrix components, have been implicated in the regulation of Shh signaling by modulating the availability of Shh ligands

Fibroblast Growth Factors (FGFs)

  • Family of signaling molecules that interact with the Sonic Hedgehog pathway in various developmental processes

TGF-b (Transforming Growth Factor-beta)

  • Shown to interact with the Sonic Hedgehog pathway in certain contexts, influencing cell fate decisions during development

Leptin

  • Hormone involved in appetite regulation, has been reported to modulate Shh signaling in certain cellular contexts

Adenosine

  • Nucleoside, has been studied for its role in Shh signaling modulation, particularly in the context of neural stem cell proliferation

Thrombospondins

  • Extracellular matrix proteins that have been implicated in Shh signaling modulation, particularly in the context of angiogenesis

Glypicans

  • Are cell surface heparan sulfate proteoglycans that can interact with Shh ligands and influence Shh signaling

Vascular Endothelial Growth Factor (VEGF)

  • VEGF, a key regulator of angiogenesis, has been reported to interact with Shh signaling, particularly in the context of blood vessel formation

Brain-Derived Neurotrophic Factor (BDNF)

  • BDNF, a neurotrophin, has been suggested to influence Shh signaling in certain neural contexts, contributing to neurodevelopment

Matrix Metalloproteinases (MMPs)

  • Enzymes involved in extracellular matrix remodeling, have been associated with the regulation of Shh signaling in certain tissues

IL-6

  • Modulate Shh signaling in different cellular contexts

Hypoxia-Inducible Factors (HIFs)

  • Transcription factors activated under low-oxygen conditions, have been linked to Shh signaling in processes like neural stem cell maintenance

Growth Hormone (GH)

  • Interact with Shh signaling in certain tissues, impacting growth and development

WISP Proteins (Wnt1-Inducible Signaling Pathway Proteins)

  • Implicated in crosstalk between the Shh and Wnt signaling pathways

MAP kinases (Mitogen-Activated Protein Kinases) and PKA (Protein Kinase A)

  • Implicated in the regulation of Shh signaling

Serotonin

  • Modulate Shh signaling in certain developmental processes, including neural tube formation

Fatty acid synthase

  • Regulate Shh signaling in certain contexts, particularly in cancer cells

Neuregulin-1 (NRG1)

  • Signaling molecule involved in neural development, has been associated with Shh signaling in certain studies

Primary cilia

  • Cellular structures essential for Shh signal transduction, are themselves regulated by various factors that impact Shh signaling

Retinoid X Receptor (RXR) Agonists

  • Explored for their potential to modulate Shh signaling, particularly in the context of neuronal differentiation

Toll-like Receptor (TLR) Ligands

Galectins

  • Carbohydrate-binding proteins, have been reported to influence Shh signaling in various cellular processes

RNA binding proteins

  • Musashi1
    • Have been implicated in the post-transcriptional regulation of Shh signaling components

Patched-Related Proteins (PTRs)

  • PTRs are homologs of the Ptch receptor and have been investigated for their roles in regulating Shh signaling

Histone Acetyltransferases (HATs) and Histone Deacetylases (HDACs)

  • Enzymes involved in histone modification, such as HATs and HDACs, have been associated with the regulation of Shh signaling gene expression

Nuclear Receptor COUP-TFII

  • COUP-TFII has been reported to interact with Shh signaling components, influencing developmental processes

Bone Morphogenetic Proteins (BMPs)

  • Between BMP signaling and Shh signaling have been studied, particularly in the context of neural development

Rab proteins

  • Involved in vesicle trafficking, have been implicated in the regulation of Shh signaling in certain cellular processes

Ephrin Signaling

  • Crosstalk with Shh signaling during embryonic development

SIRT1 (Sirtuin 1)

  • Member of the sirtuin family of deacetylases, has been associated with the modulation of Shh signaling in certain cellular contexts

Cyclooxygenase-2 (COX-2)

  • Influence Shh signaling in certain cancer contexts

Curcumin (Turmeric)

  • Curcumin, a compound found in turmeric, has been studied for its potential modulatory effects on Shh signaling in certain contexts

Resveratrol (Red Grapes, Red Wine)

  • Resveratrol, found in red grapes and red wine, has been explored for its influence on Shh signaling

Epigallocatechin Gallate (EGCG - Green Tea)

  • EGCG, a polyphenol found in green tea, has been investigated for its potential impact on Shh signaling in specific cellular models

Quercetin (Found in Fruits and Vegetables)

  • Quercetin, a flavonoid present in various fruits and vegetables, has been studied for its potential effects on Shh signaling

Omega-3 Fatty Acids

  • Found in fish oil and certain nuts, have been suggested to modulate Shh signaling in specific cellular contexts



Zákaz komnzumace potravin s přidaným glutamátem

  • Loss of expression of the anti-amyloidogenic chaperone DNAJB6
    • Upon glutamate treatment, aggregates form in neurons
  • = v.s. prevence neurodegenerativních chorob (Parkinson, Huntingtonova ch., Alzheimerova ch. další slabost)

V.s. zvýšená citlovst k nadbytku vápníku a deficitu hořčíku


Upregulace HsP40 - heat shock protein Hsp40/DNAJ family

Salicylates

  • Salicylates, which are derivatives of salicylic acid, have been reported to induce heat shock protein expression.

Curcumin in turmeric

  • Studied for its anti-inflammatory and antioxidant properties. It has been reported to induce the expression of heat shock proteins, including Hsp40.

Stimulaton of ATPase activity of HSP70

Resveratrol (Red Grapes, Red Wine)

  • Studied for its potential health benefits. It has been reported to induce the heat shock response and upregulate heat shock proteins.

Quercetin (Fruits and Vegetables)

  • Antioxidant properties and has been investigated for its ability to induce heat shock proteins.

Ginsenosides (Panax Ginseng):

  • Bioactive compounds found in Panax ginseng, have been studied for their adaptogenic properties. Some studies suggest that ginsenosides may induce heat shock proteins.

Withania somnifera (Ashwagandha):

  • Ashwagandha, an adaptogenic herb, has been investigated for its potential to modulate the heat shock response. Some studies suggest that Ashwagandha extracts may induce heat shock proteins.

Ginkgo biloba:

  • Herbal supplement, has been studied for its effects on cognitive function. There is some evidence suggesting that Ginkgo biloba extract may induce heat shock proteins.

Green Tea Polyphenols:

  • Polyphenols present in green tea, such as epigallocatechin gallate (EGCG), have been studied for their antioxidant properties. Some studies have explored their potential to induce heat shock proteins.

Silymarin (Milk Thistle):

  • Derived from milk thistle, has been investigated for its hepatoprotective effects. It has been reported to induce heat shock proteins in certain experimental settings.

Epigallocatechin Gallate (EGCG):

  • EGCG is a polyphenol found in green tea. It has been investigated for its antioxidant properties and its ability to induce heat shock proteins.

Celastrol:

  • Compound derived from traditional Chinese medicine, known for its anti-inflammatory and antioxidant properties. It has been reported to induce the heat shock response.

Trehalose:

  • Disaccharide sugar that has been studied for its ability to enhance cellular stress resistance. It may induce the expression of heat shock proteins.

4-Octyl Itaconate:

  • Derivative of itaconic acid and has been investigated for its anti-inflammatory properties. It has been reported to induce the expression of heat shock proteins.

Arbutin:

  • Glycoside found in certain plants like bearberry, has been investigated for its potential to induce the heat shock response.

Caffeine:

  • Stimulant found in coffee and tea, has been studied for its effects on the heat shock response. It may induce the expression of heat shock proteins.

Ursolic Acid:

  • Triterpenoid compound found in various plants, including apple peels. It has been studied for its potential health benefits and its ability to induce heat shock proteins.

Geranylgeranylacetone (GGA):

  • Synthetic compound that has been explored for its ability to induce the heat shock response. It has been studied in the context of stress-related conditions.

Prostaglandin J2 (PGJ2):

  • Derivative of prostaglandin, has been investigated for its anti-inflammatory effects and its potential to induce heat shock proteins.

Geranylgeranylacetone (GGA):

  • Synthetic acyclic isoprenoid, has been explored for its ability to induce heat shock proteins. It has been studied in the context of neuroprotection and stress response.

Polyunsaturated Fatty Acids (PUFAs):

  • Omega-3 polyunsaturated fatty acids, such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), found in fish oil, have been investigated for their potential to induce heat shock proteins and exert neuroprotective effects.

Arachidonic Acid (AA):

  • Omega-6 polyunsaturated fatty acid, has been studied for its role in heat shock response and inflammation. It may modulate the expression of heat shock proteins.

17-AAG (17-Allylamino-17-demethoxygeldanamycin):

  • Derivative of geldanamycin and belongs to the class of Hsp90 inhibitors. It has been studied for its ability to induce the heat shock response.

Tanshinone IIA (Salvia miltiorrhiza):

  • Bioactive compound from the root of Salvia miltiorrhiza. It has been investigated for its anti-inflammatory properties and potential to induce heat shock proteins.

Andrographolide (Andrographis paniculata):

  • Bioactive compound derived from the herb Andrographis paniculata. It has been studied for its anti-inflammatory effects and its ability to induce heat shock proteins.

Dehydroepiandrosterone (DHEA):

  • Steroid hormone precursor that has been explored for its potential to induce the heat shock response. It has been studied in the context of aging and stress resistance.

Spermidine:

  • Polyamine compound, has been investigated for its potential to induce autophagy and the heat shock response. It is found in various foods, including wheat germ and soybeans.

Quinones (e.g., Coenzyme Q10):

  • Coenzyme Q10, have been studied for their potential to induce heat shock proteins and provide antioxidant benefits.

Honokiol (Magnolia officinalis):

  • In the bark of Magnolia officinalis. It has been studied for its anti-inflammatory and neuroprotective effects, including the induction of heat shock proteins.

Melatonin

  • Regulates sleep-wake cycles, has been investigated for its antioxidant and cytoprotective effects. It has been reported to induce heat shock proteins.

Phenethyl Isothiocyanate (PEITC):

  • Found in cruciferous vegetables such as broccoli and cabbage. It has been studied for its anti-cancer properties and its ability to induce heat shock proteins.

Sulforaphane (Cruciferous Vegetables):

  • Cruciferous vegetables like broccoli, is known for its antioxidant and anti-inflammatory properties. It has been studied for its potential to induce the heat shock response.

Berberine (Berberis vulgaris):

  • In various plants including Berberis vulgaris, has been studied for its anti-inflammatory effects and its ability to induce heat shock proteins.

Carnosine

  • Of beta-alanine and histidine
  • Antioxidant properties and its potential to induce heat shock proteins.

Astaxanthin (Microalgae, Seafood):

  • Carotenoid found in microalgae and seafood. It has been investigated for its antioxidant effects and its ability to induce the heat shock response.

Betaine (Beets, Spinach):

  • Found in beets and spinach, has been studied for its potential to induce heat shock proteins and protect cells from stress.

Hesperidin (Citrus Fruits):

  • Flavonoid found in citrus fruits. It has been explored for its antioxidant and anti-inflammatory properties and its potential to induce heat shock proteins.

Tocotrienols (Vitamin E):

  • Studied for their antioxidant effects. They may also play a role in the induction of heat shock proteins.

Salidroside (Rhodiola rosea):

  • Compound found in Rhodiola rosea. It has been investigated for its adaptogenic and cytoprotective properties, including the induction of heat shock proteins.

Trehalose:

  • Disaccharide sugar composed of two glucose molecules. It has been studied for its ability to enhance cellular stress resistance and induce the heat shock response.

D-Glucose:

4-phenylbutyrate (4-PBA)

Trimethylamine N-oxide (TMAO)

Tanshinone IIA:

  • Bioactive compound from the root of Salvia miltiorrhiza and has been investigated for its anti-inflammatory properties and potential to induce HSPs.

Green tea extract

  • Rich in polyphenols such as epigallocatechin gallate (EGCG), has been investigated for its ability to induce HSP expression without causing toxicity.

Dihydrocapsaicin (DHC):

  • Compound found in chili peppers and has been studied for its potential to induce HSPs with relatively low toxicity.

Celastrol (from Thunder God Vine):

  • Triterpenoid compound derived from Thunder God Vine, has been reported to induce HSPs and has been studied for its anti-inflammatory effects with consideration for potential toxicity.

Carnosine:

  • Dipeptide composed of beta-alanine and histidine. It has been investigated for its antioxidant properties and potential to induce HSPs without significant toxicity.

Luteolin:

  • Flavonoid found in various fruits and vegetables. It has been studied for its anti-inflammatory properties and potential to induce HSP expression.

Diallyl Disulfide (from Garlic):

  • Sulfur-containing compound found in garlic. It has been reported to induce HSP expression and has been studied for its potential health benefits with low toxicity.

Alpha-Lipoic Acid:

  • Antioxidant that has been investigated for its potential to induce HSPs and protect cells from stress without causing significant toxicity.

Cyanidin-3-Glucoside (C3G):

  • Anthocyanin found in berries. It has been studied for its antioxidant effects and potential to induce HSPs without significant toxicity.

Taurine:

  • Amino acid with antioxidant properties. It has been investigated for its potential to induce HSP expression without causing significant toxicity.

Chlorogenic Acid:

  • Polyphenol found in coffee, fruits, and vegetables. It has been studied for its antioxidant effects and potential to induce HSPs without significant toxicity.

Melatonin:

  • Hormone that regulates sleep-wake cycles. It has been reported to induce HSP expression and has been studied for its potential protective effects with low toxicity.

Baicalein (from Scutellaria baicalensis):

  • Flavonoid found in the roots of Scutellaria baicalensis (Chinese skullcap). It has been studied for its antioxidant and anti-inflammatory properties, and it may induce HSP expression.

Fisetin (found in strawberries and other fruits):

  • Studied for its antioxidant and anti-inflammatory effects and potential to induce HSPs with low toxicity.

Apigenin (found in parsley, chamomile, and other plants):

  • Flavonoid found in various plants, including parsley and chamomile. It has been investigated for its anti-inflammatory properties and its potential to induce HSP expression.

Beta-Glucans (found in oats, barley, and mushrooms):

  • Polysaccharides found in oats, barley, and mushrooms. They have been studied for their immunomodulatory effects and potential to induce HSPs.

N-Acetylcysteine (NAC):

  • Precursor to the amino acid cysteine and is known for its antioxidant properties. It has been investigated for its potential to induce HSP expression without significant toxicity.

Ganoderma lucidum (Reishi Mushroom) Extract:

  • Studied for its potential health benefits. Extracts from this mushroom may induce HSPs without causing significant toxicity.

Boswellic Acid (from Boswellia serrata):

  • Compound found in the resin of Boswellia serrata. It has been reported to have anti-inflammatory properties and may induce HSPs.

Sophoricoside (from Sophora japonica):

  • Studied for its antioxidant effects and potential to induce HSP expression.

Citrus Limonoids (found in citrus fruits):

  • Investigated for their potential health benefits, including antioxidant effects and induction of HSPs.

Cucurbitacin E (found in various vegetables):

  • Triterpenoid compound found in various vegetables. It has been studied for its potential anti-inflammatory effects and induction of HSPs.

Allicin (found in garlic):

  • Released when garlic is crushed or chopped. It has been reported to have antioxidant properties and may induce HSP expression.




Insulin-like growth factor 1 (IGF-1)

  • Essential hormone with crucial roles in growth, development, and overall cellular function.
  • While a deficit in IGF-1 can lead to growth-related issues, including short stature, there is evidence suggesting that alterations in IGF-1 signaling may be associated with neurological and cognitive outcomes, including potential effects on brain development.

Neurotrophic Effects of IGF-1:

  • IGF-1 is known to have neurotrophic effects, promoting the survival, growth, and differentiation of neurons. Insufficient IGF-1 signaling during critical periods of brain development could potentially contribute to structural abnormalities.

Neurodevelopmental Disorders:

  • Altered IGF-1 signaling has been implicated in certain neurodevelopmental disorders.
  • Research has suggested associations between IGF-1 dysregulation and conditions such as autism spectrum disorder (ASD) and intellectual disabilities.

Animal Studies:

  • Mice with disruptions in the IGF-1 pathway
    • Have shown changes in brain structure and function, including alterations in synaptic plasticity.

Clinical Conditions:

  • Clinical conditions associated with IGF-1 deficiency, such as Laron syndrome (a rare form of growth hormone insensitivity)
    • Reported to involve not only growth-related issues but also potential cognitive and neurological effects.
  • Takže na základě tady toho rychlého orientačního nálezu bych se nebála zkusit hledat přijatelnou aplikaci IGF-1 do nosu, kudy pronikne do mozku a může podpořit neurolgický vývoj.


Sledování a časná kompenzace klinického obrazu

  • GIT, močový systém - nemít infekce a zácpu
  • Kontrola hormonů a případná kompenzace = má vliv i na vývoj mozku
  • Opatrnost na krční páteř - nedělat nevhodné sporty, kde hrozí zhmoždění/úraz
  • Zdravé prostředí a strava - vyšší citlivost ke kancerogenům v.s.
  • Prevence deficitu vitamínu D - je to nervový růstový hormon


Upregulation of DPPX signalizace na zbývající druhé kopii chromozomu 7

Transcription factors and regulatory elements in the gene's promoter region

  • Play a role in controlling DPPX expression

Epigenetic modifications

  • DNA methylation and histone acetylation, can regulate gene expression

Post-transcriptional processes

  • Alternative splicing and RNA stability
  • Can impact the abundance of DPPX mRNA

Protein Stability and Degradation:

Cellular Signaling Pathways:

  • Activation of specific pathways or receptors
    • May lead to the upregulation of DPPX

External factors

Pharmacological Interventions:

Neuropeptide Y (NPY) or glutamate.

  • Modulate ion channels, particularly those involved in neuronal function, might have downstream effects on DPPX.
    • Includes potassium channel modulators, sodium channel modulators, or compounds affecting other ion channels.

Neurotrophic Factors:

  • That promote neuronal growth and survival might impact DPPX expression or function indirectly.

Ligands for G protein-coupled receptors (GPCRs)

  • Expressed in neurons could potentially influence DPPX signaling.
  • GPCRs play a role in various signaling cascades.

Neurosteroids

  • Endogenous steroids synthesized in the brain
  • Can modulate ion channels and neurotransmitter receptors
  • Some might influence neuronal function and potentially affect DPPX.

Cannabinoids:

  • Compounds that interact with the endocannabinoid system
  • Might influence neuronal signaling and could have downstream effects on DPPX.

Modulators of Intracellular Calcium Levels:

  • Compounds that influence intracellular calcium levels may impact DPPX signaling.
    • calcium channel modulators
    • Regulators of calcium release from intracellular stores

Glycine Receptor Modulators:

  • Glycine receptors play a role in inhibitory neurotransmission.
  • Compounds that modulate glycine receptors might affect neuronal excitability and could have downstream effects on DPPX.

Neuronal Nitric Oxide Synthase (nNOS) Modulators:

  • Modulators of nNOS involved in nitric oxide production in neurons
    • Might influence neuronal signaling and potentially impact DPPX.

Glutamate Receptor Modulators:

  • Compounds that modulate glutamate receptors, including NMDA receptors or AMPA receptors
  • May influence synaptic transmission and could have downstream effects on DPPX.

Physical Exercise

  • Regular aerobic exercise has been linked to an upregulation of potassium channels, including Kv4.2.

Brain-Derived Neurotrophic Factor (BDNF)

  • Increase BDNF, such as aerobic exercise and certain cognitive activities
    • May contribute to the upregulation of Kv4.2 channels.

Neurotrophins

  • Some like brain-derived neurotrophic factor (BDNF)
    • Associated with the upregulation of potassium channels
  • Activities that stimulate the release of neurotrophins, such as exercise and certain learning activities, may be beneficial.

Neuronal Activity and synaptic transmission

  • Can influence the expression and function of potassium channels.

Omega-3 Fatty Acids

  • Some studies suggest that omega-3 fatty acids, found in fish oil and certain nuts, may have a positive impact on ion channel function, although the specific effects on Kv4.2 channels may not be well-documented.

Curcumin

  • Studied for its potential neuroprotective effects and modulation of ion channels.

Resveratrol

  • Red grapes and wine, resveratrol has been investigated for its potential to modulate ion channels, although its effects on Kv4.2 specifically may need further research.

Caloric Restriction

  • Some studies suggest that caloric restriction and intermittent fasting may have positive effects on ion channel function, including potassium channels. This could potentially influence the upregulation of Kv4.2.

Cognitive Stimulation

  • Engaging in activities that stimulate the brain, such as learning new skills or engaging in intellectually challenging tasks, may promote the upregulation of potassium channels.

Adequate Sleep

  • Sleep is crucial for overall brain health, and disruptions in sleep patterns have been associated with changes in ion channel function. Ensuring sufficient and quality sleep may contribute to the upregulation of Kv4.2 channels.

Antioxidants

  • Foods rich in antioxidants, such as fruits and vegetables, may support neuronal health and potentially influence potassium channel expression.

Polyunsaturated Fatty Acids (PUFAs)

  • Omega-3 fatty acids, particularly docosahexaenoic acid (DHA), found in fish oil, have been associated with improved neuronal function and may play a role in ion channel modulation.

Lithium

  • Mood stabilizer that has been suggested to modulate ion channels, including potassium channels.
  • However, its precise effects on Kv4.2 may require further investigation.

Quercetin

  • This flavonoid found in various fruits and vegetables has antioxidant properties and has been studied for its potential neuroprotective effects. While its specific impact on Kv4.2 channels is not well-established, it may contribute to overall neuronal health.

Taurine

  • An amino acid with antioxidant properties, taurine has been investigated for its neuroprotective effects and potential modulation of ion channels.

Epigallocatechin Gallate (EGCG)

  • Found in green tea, EGCG is a polyphenol with antioxidant properties. Some studies suggest it may have neuroprotective effects, but its impact on Kv4.2 channels specifically would require more research.

Puerarin

  • This compound, found in the kudzu root, has been studied for its potential neuroprotective effects and modulation of ion channels.

Inhibition of Hsp70

Neuritin

  • Up-regulates Kv4.2 a-Subunit of Potassium Channel Expression
  • Affects Neuronal Excitability by Regulating the Calcium-Calcineurin-NFATc4 Signaling Pathway
  • Neurotrophin
  • Regulates neural development, synaptic plasticity, and neuronal survival.
  • Applications of neuritin in neuronal dysfunctions
  • Neuritin upregulates transient potassium outward current (IA) subunit Kv4.2 expression
    • Increases IA densities
      • Activating the insulin receptor (IR) signaling pathway
  • Ca2+/calcineurin (CaN)/Nuclear Factor of Activated T-cells (NFAT) c4 axis
    • Required for neuritin-induced Kv4.2 transcriptional expression and potentiation of IA densities in cerebellum granule neurons (CGNs)
  • Neuritin elevates intracellular Ca2+, increases Kv4.2 expression and IA densities
    • Effect was sensitive to CaN inhibition
    • Eliminated in Nfatc4-/- mice but not in Nfatc2-/- mice
  • NFATc4 was recruited to the Kv4.2 gene promoter loci
  • www.researchgate.net/publication/304009385_Neuritin_Up-regulates_Kv42_a-Subunit_of_Potassium_Channel_Expression_and_Affects_Neuronal_Excitability_by_Regulating_the_Calcium-Calcineurin-NFATc4_Signaling_Pathway

NFATc4 stimulation


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Poslední aktualizace: 30. 11. 2023 1:39:25