Alkaline Phosphatase Offers New Hope for Inflammation Relief and Health Benefits
Nikhil Prasad Fact checked by:Thailand Medical News Team Nov 03, 2024 1 day, 10 hours, 43 minutes ago
Medical News: Researchers from the G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, and the Youth Research Laboratory of Recombinant DNA Technologies at Far Eastern Federal University in Russia have conducted a compelling study on the role of alkaline phosphatase (ALP) in reducing inflammation. This
Medical News report delves into the complex but significant findings of the study, detailing how this enzyme can help alleviate various inflammatory conditions.
Putative anti-inflammatory mechanisms of non-specific phosphomonoesterase, cellular (ALP: GPI-bound), and extracellular (eALP: exogenous or free endogenous) alkaline phosphatase on innate immune and epithelial cells: (1) Inhibition of LPS-TLR4 binding and TLR-4-NF-kB-induced pathways (IL-1, IL-2, TNF-α, TLR4, NOX2, etc., ROS production (extracellular ROS and mitochondrial mtROS) associated with immune cell recruitment (highlighted by a yellow block in the lower left corner); (2) Dephosphorylation of the intercellular signaling purine nucleotides AMP, ADP and ATP (and pyrimidines), together with the ecto-enzymes CD39, CD73 and eNPP1, to the anti-inflammatory adenosine (Ado) and phosphate ions PO42− (P), allowing Ado to bind to adenosine receptors (A2AR) and inhibit the pro-inflammatory pathways NF-kB, PI3K-Akt-mTOR and TNF-α (illustrated for neutrophil in the upper right corner) (highlighted by a rose block); (3) Dephosphorylation of nicotinamide mononucleotide (NMN) to nicotinamide riboside (NR) and NAD(P)H to NADH for de novo NAD+ synthesis and salvage pathways (highlighted by a green block); (4) Putative (?) induction and/or acceleration of the internalization of membrane-bound phosphorylated biomolecules at phosphoinositide(PI)-specific sites, which are recruited by inflammatory signals for caveolae-mediated endocytosis of LPS-bound receptors TLR4 (shown for macrophage, center), NOX1 (shown for enterocyte, top left), NOX2, PTEN (shown for macrophage, center) and other proinflammatory multimolecular factors, due to the ability of ALP (and eALP) to form “enzyme-substrate” complexes or aggregates with LPS, PIs, membrane phospholipids and transmembrane phosphoproteins (highlighted by a blue blocks); (5) dephosphorylation to activate the fatty acid translocase CD36 (receptor SR-B2) to optimize fatty acid uptake, including by caveolae-dependent endocytosis, and to activate β-oxidation and a switch from glycolysis in M1 macrophages to oxidative phosphorylation (oxphosph) in M2 macrophages (center) (highlighted by a green block); (6) participation in selective autophagy initiated from the endoplasmic reticulum (ER) and linked to the mitochondrial membrane via the PI3P site (shown for de novo synthesized ALP in the enterocyte, top left) (highlighted by a blue block).
A Multifaceted Approach to Reducing Inflammation
This study focuses on alkaline phosphatase, an enzyme present in the body and sometimes introduced externally to help manage inflammation. Inflammation, which is often associated with immune response, can cause tissue damage when left unchecked. ALP has shown to be effective in reducing inflammation related to Toll-like receptor 4 (TLR4) signaling, oxid
ative stress, and metabolic dysfunctions. The research reveals that ALP could be helpful in managing inflammatory bowel disease, liver issues, and even certain heart and kidney conditions.
Mechanisms Behind Alkaline Phosphatase’s Anti-Inflammatory Effects
In this detailed study, researchers observed that ALP acts on inflammation through multiple pathways. For instance, in the case of TLR4 signaling - an immune pathway that, when overactivated, can cause excessive inflammation - ALP works to limit the interaction between TLR4 and its signaling molecules. The enzyme achieves this by neutralizing harmful substances like lipopolysaccharides (LPS), a bacterial toxin that can trigger immune responses.
The study also highlights that ALP helps in managing oxidative stress. Oxidative stress, a damaging process resulting from an imbalance of free radicals in the body, can exacerbate inflammation and lead to severe tissue damage. ALP, by reducing the level of oxidative stress, mitigates these negative impacts and aids in preserving cell health.
Impact on the Immune System
Beyond merely controlling inflammation, ALP influences immune responses. ALP appears to deactivate certain molecules that stimulate pro-inflammatory signals, thereby preventing overactivation of immune cells. This selective deactivation, achieved through dephosphorylation (removal of phosphate groups), stops the cascade of inflammation and preserves the integrity of tissues.
Furthermore, ALP has been found to support cell energy regulation, allowing immune cells to adapt to inflammation without succumbing to energy depletion. In inflammatory situations, immune cells often undergo metabolic shifts to support rapid energy requirements. ALP helps cells switch from energy-consuming to energy-saving modes, which prolongs cell survival and function in inflamed tissues.
Gut Health and Systemic Benefits
The study also points out the relevance of ALP in gut health. Alkaline phosphatase is active in the gut, where it dephosphorylates harmful bacterial products, thereby limiting the immune system’s exposure to them. The gut acts as a frontline barrier in preventing harmful substances from entering the bloodstream. ALP in the gut significantly reduces inflammation by neutralizing LPS and enhancing the barrier function of the intestinal lining. This is especially relevant in conditions like colitis, where an overactive immune response in the gut can lead to chronic inflammation.
Alkaline Phosphatase’s Role in Metabolic Health
The researchers further observed ALP's effects on metabolic health, particularly in conditions linked to metabolic syndrome. Metabolic syndrome encompasses a group of risk factors, including high blood pressure, high blood sugar, and unhealthy cholesterol levels. ALP, according to the study, helps maintain insulin sensitivity and prevent metabolic dysfunctions. In mouse models, the enzyme improved glucose metabolism and reduced oxidative damage in the liver, kidneys, and heart, which suggests its potential as a therapeutic target for metabolic syndrome.
A Potential New Pathway for Drug Development
Based on the findings, ALP may play an essential role in the development of future anti-inflammatory medications. By targeting pathways that ALP naturally influences, scientists could design drugs that provide similar anti-inflammatory benefits without the need for synthetic chemicals. Since ALP can reduce inflammation without entirely suppressing immune responses, it could be safer than current anti-inflammatory drugs that often compromise immune function.
Conclusion: Expanding Our Understanding of ALP’s Therapeutic Potential
In conclusion, the study shines a spotlight on alkaline phosphatase as a multifunctional enzyme with considerable promise in managing inflammation. Its ability to modulate immune responses without damaging healthy cells provides a safer alternative for treating chronic inflammatory diseases. ALP's anti-inflammatory effects extend beyond simply reducing inflammation; it also restores metabolic balance and cellular health, making it a valuable asset for managing not only inflammatory diseases but also metabolic syndrome.
The findings present new avenues for therapeutic interventions. Alkaline phosphatase, whether administered as an external treatment or supported through dietary and lifestyle factors that enhance its natural production, could potentially transform the treatment landscape for patients with chronic inflammatory and metabolic conditions. Its potential is especially relevant in modern medicine as chronic inflammation is increasingly linked to a variety of diseases, from metabolic syndrome to cardiovascular ailments.
The study findings were published in the peer-reviewed journal: Biomedicines.
https://www.mdpi.com/2227-9059/12/11/2502
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