\u0425\u0440\u043e\u043d\u0438\u0447\u043d\u0430\u0442\u0430, \u043d\u0438\u0441\u043a\u0430 \u0441\u0442\u0435\u043f\u0435\u043d \u043d\u0430 \u0432\u044a\u0437\u043f\u0430\u043b\u0435\u043d\u0438\u0435 \u0432\u0435\u0447\u0435 \u0435 \u043f\u0440\u0438\u0437\u043d\u0430\u0442\u0430 \u043a\u0430\u0442\u043e \u043e\u0441\u043d\u043e\u0432\u043d\u0430 \u043f\u0440\u0438\u0447\u0438\u043d\u0430 \u0437\u0430\u0434 \u0440\u0435\u0434\u0438\u0446\u0430 \u0445\u0440\u043e\u043d\u0438\u0447\u043d\u0438 \u0434\u0435\u0433\u0435\u043d\u0435\u0440\u0430\u0442\u0438\u0432\u043d\u0438 \u0441\u044a\u0441\u0442\u043e\u044f\u043d\u0438\u044f, \u0432\u043a\u043b\u044e\u0447\u0438\u0442\u0435\u043b\u043d\u043e \u0441\u044a\u0440\u0434\u0435\u0447\u043d\u043e-\u0441\u044a\u0434\u043e\u0432\u0438 \u0437\u0430\u0431\u043e\u043b\u044f\u0432\u0430\u043d\u0438\u044f, \u0434\u0438\u0430\u0431\u0435\u0442, \u0440\u0430\u043a, \u0410\u043b\u0446\u0445\u0430\u0439\u043c\u0435\u0440, \u041f\u0430\u0440\u043a\u0438\u043d\u0441o\u043d \u0438 \u0434\u0440. \u041e\u0444\u0438\u0446\u0438\u0430\u043b\u043d\u0430\u0442\u0430 \u043c\u0435\u0434\u0438\u0446\u0438\u043d\u0430 \u0442\u0432\u044a\u0440\u0434\u0438, \u0447\u0435 \u043f\u0440\u0438\u0447\u0438\u043d\u0430\u0442\u0430 \u0437\u0430 \u0442\u0430\u0437\u0438 \u0445\u0440\u043e\u043d\u0438\u0447\u043d\u0430, \u043d\u0438\u0441\u043a\u0430 \u0441\u0442\u0435\u043f\u0435\u043d \u043d\u0430 \u0432\u044a\u0437\u043f\u0430\u043b\u0435\u043d\u0438\u0435 \u0435 \u043d\u0435\u0438\u0437\u0432\u0435\u0441\u0442\u043d\u0430, \u0432\u044a\u043f\u0440\u0435\u043a\u0438 \u0434\u043e\u0431\u0440\u0435 \u0438\u0437\u0432\u0435\u0441\u0442\u043d\u0430\u0442\u0430 \u0440\u043e\u043b\u044f, \u043a\u043e\u044f\u0442\u043e \u041f\u0423\u0424\u0410 \u0438\u0433\u0440\u0430\u044f\u0442 \u043a\u0430\u0442\u043e \u043f\u0440\u0435\u043a\u0443\u0440\u0441\u043e\u0440\u0438 \u043d\u0430 \u043d\u0430\u0439-\u0432\u0430\u0436\u043d\u0438\u0442\u0435 \u0432\u044a\u0437\u043f\u0430\u043b\u0438\u0442\u0435\u043b\u043d\u0438 \u043f\u043e\u0441\u0440\u0435\u0434\u043d\u0438\u0446\u0438 (\u043f\u0440\u043e\u0441\u0442\u0430\u0433\u043b\u0430\u043d\u0434\u0438\u043d\u0438 \u0438 \u043b\u0435\u0439\u043a\u043e\u0442\u0440\u0438\u0435\u043d\u0438). \u0418\u0437\u0441\u043b\u0435\u0434\u0432\u0430\u043d\u0435\u0442\u043e \u043f\u043e-\u0434\u043e\u043b\u0443 \u0434\u043e\u0431\u0430\u0432\u044f \u0445\u0440\u043e\u043d\u0438\u0447\u043d\u0438\u044f \u0441\u0442\u0440\u0435\u0441 \u0438 \u043f\u0440\u0438\u0447\u0438\u043d\u0435\u043d\u0438\u0442\u0435 \u043e\u0442 \u043d\u0435\u0433\u043e \u0443\u0432\u0440\u0435\u0436\u0434\u0430\u043d\u0438\u044f \u043d\u0430 \u043c\u0438\u0442\u043e\u0445\u043e\u043d\u0434\u0440\u0438\u0438\u0442\u0435, \u043a\u0430\u0442\u043e \u0433\u043b\u0430\u0432\u043d\u0438 \u0444\u0430\u043a\u0442\u043e\u0440\u0438 \u0437\u0430 \u0445\u0440\u043e\u043d\u0438\u0447\u043d\u0430\u0442\u0430 \u0432\u044a\u0437\u043f\u0430\u043b\u0438\u0442\u0435\u043b\u043d\u0430 \u0440\u0435\u0430\u043a\u0446\u0438\u044f. \u0412\u044a\u043f\u0440\u0435\u043a\u0438 \u0447\u0435 \u043f\u043e\u043f\u0443\u043b\u044f\u0440\u043d\u0430\u0442\u0430 \u043f\u0440\u0435\u0441\u0430 \u043d\u0435 \u0441\u043f\u043e\u043c\u0435\u043d\u0430\u0432\u0430 \u0442\u043e\u0432\u0430, \u0440\u0435\u0430\u043b\u043d\u043e\u0442\u043e \u0438\u0437\u0441\u043b\u0435\u0434\u0432\u0430\u043d\u0435 \u043f\u043e\u043a\u0430\u0437\u0432\u0430, \u0447\u0435 \u0432\u044a\u0437\u043f\u0430\u043b\u0438\u0442\u0435\u043b\u043d\u0438\u044f\u0442 \u043a\u0430\u0441\u043a\u0430\u0434 \u0437\u0430\u043f\u043e\u0447\u0432\u0430 \u0441 \u0435\u043d\u0434\u043e\u0442\u043e\u043a\u0441\u0438\u043d (LPS) \u0438 \u0432\u043a\u043b\u044e\u0447\u0432\u0430 \u0443\u0432\u0435\u043b\u0438\u0447\u0435\u043d \u043f\u0440\u0438\u0435\u043c \u043d\u0430 \u0445\u043e\u043b\u0438\u043d \u043e\u0442 \u043a\u043b\u0435\u0442\u043a\u0438\u0442\u0435. \u0411\u043b\u043e\u043a\u0438\u0440\u0430\u043d\u0435\u0442\u043e \u043d\u0430 \u0435\u0444\u0435\u043a\u0442\u0438\u0442\u0435 \u043d\u0430 \u0435\u043d\u0434\u043e\u0442\u043e\u043a\u0441\u0438\u043d\u0430 (\u0447\u0440\u0435\u0437 TLR4) \u0438\u043b\u0438 \u043f\u0440\u0438\u0435\u043c\u0430 \u043d\u0430 \u0445\u043e\u043b\u0438\u043d \u043f\u0440\u0435\u043a\u044a\u0441\u0432\u0430 \u0432\u044a\u0437\u043f\u0430\u043b\u0438\u0442\u0435\u043b\u043d\u0438\u044f \u043e\u0442\u0433\u043e\u0432\u043e\u0440. \u0414\u0440\u0443\u0433 \u0432\u044a\u0437\u043c\u043e\u0436\u0435\u043d \u043f\u043e\u0434\u0445\u043e\u0434 \u0435 \u043f\u0440\u0438\u043b\u0430\u0433\u0430\u043d\u0435\u0442\u043e \u043d\u0430 \u043b\u0438\u0442\u0438\u0439 \u0438\u043b\u0438 \u043d\u0430\u0442\u0440\u0438\u0439, \u043a\u043e\u0438\u0442\u043e \u043c\u043e\u0433\u0430\u0442 \u0434\u0430 \u043f\u0440\u0435\u0434\u0438\u0437\u0432\u0438\u043a\u0430\u0442 \u043c\u0438\u0442\u043e\u0444\u0430\u0433\u0438\u044f \u0432 \u043e\u0442\u0441\u043b\u0430\u0431\u0435\u043d\u0438 \u0438\u043b\u0438 \u043f\u043e\u0432\u0440\u0435\u0434\u0435\u043d\u0438 \u043c\u0438\u0442\u043e\u0445\u043e\u043d\u0434\u0440\u0438\u0438.<\/p>\n\n\n\n
https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/24398558<\/a><\/p>\n\n\n\n However, considering the fact that both lithium and sodium are frowned upon by both Big Pharma and regulatory agencies like FDA, it is unlikely that any of these cheap, safe interventions will ever become part of the mainstream medical approach.<\/p>\n\n\n\n https:\/\/www.sciencedirect.com\/science\/article\/pii\/S1550413119301391?via%3Dihub<\/a><\/p>\n\n\n\n \u201c\u2026Choline<\/a> is a vitamin-like nutrient that is taken up via specific transporters and metabolized by choline kinase<\/a>, which converts it to phosphocholine<\/a> needed for de novo<\/em> synthesis of phosphatidylcholine<\/a> (PC), the main phospholipid<\/a> of cellular membranes. We found that <\/strong>Toll-like receptor<\/strong><\/a> (TLR) activation enhances <\/strong>choline<\/strong><\/a>uptake by macrophages and <\/strong>microglia<\/strong><\/a> through induction of the choline transporter CTL1. Inhibition of CTL1 expression or choline <\/strong>phosphorylation<\/strong><\/a> attenuated NLRP3 <\/strong>inflammasome<\/strong><\/a> activation and IL-1\u03b2 and <\/strong>IL-18<\/strong><\/a> production in stimulated macrophages.<\/strong> Mechanistically, reduced choline uptake<\/a> altered mitochondrial lipid profile<\/a>, attenuated mitochondrial ATP<\/a> synthesis, and activated the energy sensor AMP-activated protein kinase<\/a> (AMPK). By potentiating mitochondrial recruitment of DRP1, AMPK stimulates mitophagy<\/a>, which contributes to termination of NLRP3 inflammasome activation. Correspondingly, choline kinase inhibitors ameliorated acute and chronic models of IL-1\u03b2-dependent inflammation<\/strong>.\u201d<\/p>\n\n\n\n https:\/\/phys.org\/news\/2019-04-mice-mitochondria-alleviates-chronic-inflammatory.html<\/a><\/p>\n\n\n\n \u201c\u2026Inflammation is a balanced physiological response\u2014the body needs it to eliminate invasive organisms and foreign irritants, but excessive inflammation can harm healthy cells, contributing to aging and chronic diseases. To help keep tabs on inflammation, immune cells employ a molecular machine called the NLRP3 inflammasome. NLRP3 is inactive in a healthy cell, but is switched \u201con\u201d when the cell\u2019s mitochondria (energy-generating organelles) are damaged by stress or exposure to bacterial toxins<\/strong>. However, when the NLRP3 inflammasome gets stuck in the \u201con\u201d position, it can contribute to a number of chronic inflammatory conditions, including gout, osteoarthritis, <\/strong>fatty liver disease<\/strong><\/a> and Alzheimer\u2019s and Parkinson\u2019s diseases<\/strong>. \u201c<\/p>\n\n\n\n \u201c\u2026In a 2018 study published in Nature, Karin\u2019s team had shown that damaged mitochondria activate the NLRP3 inflammasome. The researchers also found that the NLRP3 inflammasome is de-activated when mitochondria are removed by the cell\u2019s internal waste recycling process, called mitophagy<\/strong>.\u201d After that, we wondered if we could reduce harmful excess inflammation by intentionally inducing mitophagy, which would eliminate damaged mitochondria and should in turn pre-emptively inhibit NLRP3 inflammasome activation,\u201d Karin said. \u201cBut at the time we didn\u2019t have a good way to induce mitophagy.\u201d More recently, Sanchez-Lopez was studying how macrophages regulate their uptake of choline, a nutrient critical for metabolism<\/strong>, when she discovered something that can initiate mitophagy: an inhibitor of the enzyme choline kinase (ChoK). With ChoK inhibited, choline is no longer incorporated into mitochondrial membranes. As a result, the cells perceive the mitochondria as damaged, and cleared them away by mitophagy<\/strong>. \u201cMost importantly, by getting rid of damaged mitochondria<\/a> with ChoK inhibitors, we were finally able to inhibit NLRP3 inflammasome activation,\u201d Karin said. To test their new ability to control NLRP3 inflammasome in a living system, the researchers turned to mice. They discovered that treatment with ChoK inhibitors prevented acute inflammation caused by uric acid (accumulation of which triggers gout flares) and a bacterial toxin. By several measures, ChoK inhibitor treatment also reversed chronic inflammation associated with a genetic disease<\/strong> called Muckle-Well Syndrome, which is caused by mutations in NLRP3 genes. One such measure is spleen size\u2014the larger the spleen, the more inflammation. The spleens of Muckle-Well Syndrome mice are on average twice as large as normal mice, but their spleen sizes normalized after ChoK inhibitor treatment.\u201d<\/p>\n\n\n\n https:\/\/medicalxpress.com\/news\/2016-02-molecular-excessive-inflammation.html<\/a><\/p>\n\n\n\n \u201c\u2026However, foreign particles don\u2019t act directly on the NLRP3-inflammasome. Instead, Karin\u2019s team found, foreign particles damage the macrophage\u2019s mitochondria\u2014the cell\u2019s energy-producing \u201cpower plant.\u201d In turn, damaged mitochondria release signals that activate the NLRP3-inflammasome and keep it cranking out IL-1beta<\/strong>. That\u2019s a good thing if your body needs to clear out invading particles or microbes, but continuous production of IL-1beta is very dangerous\u2014it can easily lead to an inflammatory chain reaction that results in multi-organ failure, septic shock and death<\/strong>. The body needs a way to turn off IL-1beta production by NLRP3-inflammasomes. To do this, Karin\u2019s team discovered, macrophages responding to foreign microbes and irritants also bump up production of p62. This protein coats damaged mitochondria that release inflammasome-activating signals and ensures they are eliminated. Once these damaged mitochondria are removed, the NLRP3-inflammasome de-activates and IL-1beta production is turned off. \u201cWe\u2019ve suspected for quite some time that damage to mitochondria caused by either genetic or environmental factors is the root cause of many age-related diseases, all of which are associated with chronic, low-grade inflammation<\/strong>,\u201d said Zhong. \u201cTherefore, p62\u2014and its part in eliminating damaged mitochondria\u2014could provide a new target for preventing such diseases<\/strong>. Indeed, we already know that another protein that collaborates with p62 to eliminate damaged mitochondria is Parkin, which plays a role in a rare form of Parkinson\u2019s disease.\u201d<\/p>\n\n\n\n \u03a0\u03b7\u03b3\u03ae:<\/p>\n\n\n\n http:\/\/haidut.me\/?p=51<\/a><\/p>\n\n\n \u0425\u0440\u043e\u043d\u0438\u0447\u043d\u0430\u0442\u0430, \u043d\u0438\u0441\u043a\u0430 \u0441\u0442\u0435\u043f\u0435\u043d \u043d\u0430 \u0432\u044a\u0437\u043f\u0430\u043b\u0435\u043d\u0438\u0435 \u0432\u0435\u0447\u0435 \u0435 \u043f\u0440\u0438\u0437\u043d\u0430\u0442\u0430 \u043a\u0430\u0442\u043e \u043e\u0441\u043d\u043e\u0432\u043d\u0430 \u043f\u0440\u0438\u0447\u0438\u043d\u0430 \u0437\u0430\u0434 \u0440\u0435\u0434\u0438\u0446\u0430 \u0445\u0440\u043e\u043d\u0438\u0447\u043d\u0438 \u0434\u0435\u0433\u0435\u043d\u0435\u0440\u0430\u0442\u0438\u0432\u043d\u0438 \u0441\u044a\u0441\u0442\u043e\u044f\u043d\u0438\u044f, \u0432\u043a\u043b\u044e\u0447\u0438\u0442\u0435\u043b\u043d\u043e \u0441\u044a\u0440\u0434\u0435\u0447\u043d\u043e-\u0441\u044a\u0434\u043e\u0432\u0438 \u0437\u0430\u0431\u043e\u043b\u044f\u0432\u0430\u043d\u0438\u044f, \u0434\u0438\u0430\u0431\u0435\u0442, \u0440\u0430\u043a, \u0410\u043b\u0446\u0445\u0430\u0439\u043c\u0435\u0440, \u041f\u0430\u0440\u043a\u0438\u043d\u0441o\u043d \u0438 \u0434\u0440. \u041e\u0444\u0438\u0446\u0438\u0430\u043b\u043d\u0430\u0442\u0430 \u043c\u0435\u0434\u0438\u0446\u0438\u043d\u0430 \u0442\u0432\u044a\u0440\u0434\u0438, \u0447\u0435 \u043f\u0440\u0438\u0447\u0438\u043d\u0430\u0442\u0430 \u0437\u0430 \u0442\u0430\u0437\u0438 \u0445\u0440\u043e\u043d\u0438\u0447\u043d\u0430, \u043d\u0438\u0441\u043a\u0430 \u0441\u0442\u0435\u043f\u0435\u043d \u043d\u0430 \u0432\u044a\u0437\u043f\u0430\u043b\u0435\u043d\u0438\u0435 \u0435 \u043d\u0435\u0438\u0437\u0432\u0435\u0441\u0442\u043d\u0430, \u0432\u044a\u043f\u0440\u0435\u043a\u0438 \u0434\u043e\u0431\u0440\u0435 \u0438\u0437\u0432\u0435\u0441\u0442\u043d\u0430\u0442\u0430 \u0440\u043e\u043b\u044f, \u043a\u043e\u044f\u0442\u043e \u041f\u0423\u0424\u0410 \u0438\u0433\u0440\u0430\u044f\u0442 \u043a\u0430\u0442\u043e \u043f\u0440\u0435\u043a\u0443\u0440\u0441\u043e\u0440\u0438 \u043d\u0430 \u043d\u0430\u0439-\u0432\u0430\u0436\u043d\u0438\u0442\u0435 \u0432\u044a\u0437\u043f\u0430\u043b\u0438\u0442\u0435\u043b\u043d\u0438 \u043f\u043e\u0441\u0440\u0435\u0434\u043d\u0438\u0446\u0438 (\u043f\u0440\u043e\u0441\u0442\u0430\u0433\u043b\u0430\u043d\u0434\u0438\u043d\u0438 \u0438 \u043b\u0435\u0439\u043a\u043e\u0442\u0440\u0438\u0435\u043d\u0438). 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