Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344329 (collapse)
 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gut barrier separates trillions of microbes from the largest immune system in the body; when compromised, a "leaky" gut barrier fuels systemic inflammation, which hastens the progression of chronic diseases. Strategies to detect and repair the leaky gut barrier remain urgent and unmet needs. Recently, a stress-polarity signaling (SPS) pathway has been described in which the metabolic sensor, AMP-kinase acts via its effector, GIV (also known as Girdin) to augment epithelial polarity exclusively under energetic stress and suppresses tumor formation. Using murine and human colon-derived organoids, and enteroid-derived monolayers (EDMs) that are exposed to stressors, we reveal that the SPS-pathway is active in the intestinal epithelium and requires a catalytically active AMP-kinase. Its pharmacologic augmentation resists stress-induced collapse of the epithelium when challenged with microbes or microbial products. In addition, the SPS-pathway is suppressed in the aging gut, and its reactivation in enteroid-derived monolayers reverses aging-associated inflammation and loss of barrier function. It is also silenced during progression of colorectal cancers. These findings reveal the importance of the SPS-pathway in the gut and highlights its therapeutic potential for treating gut barrier dysfunction in aging, cancer, and dysbiosis.
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PMID:The stress polarity signaling (SPS) pathway serves as a marker and a target in the leaky gut barrier: implications in aging and cancer. 3204 49

Central nervous system injury often causes lifelong impairment of neural function, because the regenerative ability of axons is limited, making a sharp contrast to the successful regeneration that is seen in the peripheral nervous system. Nevertheless, partial functional recovery is observed, because axonal branches of damaged or undamaged neurons sprout and form novel relaying circuits. Using a lot of animal models such as the spinal cord injury model or the optic nerve injury model, previous studies have identified many factors that promote or inhibit axonal regeneration or sprouting. Molecules in the myelin such as myelin-associated glycoprotein, Nogo-A or oligodendrocyte-myelin glycoprotein, or molecules found in the glial scar such as chondroitin sulfate proteoglycans, activate RhoA signaling, which leads to the collapse of the growth cone and inhibit axonal regeneration. By contrast, axonal regeneration programs can be activated by many molecules such as regeneration-associated transcription factors, cyclic AMP, neurotrophic factors, growth factors, mechanistic target of rapamycin or immune-related molecules. Axonal sprouting and axonal regeneration largely share these mechanisms. For functional recovery, appropriate pruning or suppressing of aberrant sprouting are also important. In contrast to adults, neonates show much higher sprouting ability. Specific cell types, various mouse strains and different species show higher regenerative ability. Studies focusing on these models also identified a lot of molecules that affect the regenerative ability. A deeper understanding of the mechanisms of neural circuit repair will lead to the development of better therapeutic approaches for central nervous system injury.
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PMID:Neural circuit repair after central nervous system injury. 3327 Jan 8


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