Molecular Structure Of Alpha Klotho Revealed8 meses, 2 semanas hace
Publicado en Jul 10, 2018, 10 p.m.
Researchers from UT Southwestern published in Nature the molecular structure of alpha Klotho and how the anti-aging protein transmits a hormonal signal that controls a variety of biological processes in collaboration with the University of New York and Wenzhou University.
Mice lacking in either a-Klotho or hormone FGF23 were demonstrated 2 decades ago to suffer from premature and multiple organ failures as well as other conditions including early onset of CVD, cognitive decline, and cancer. It was inferred that a-Klothos suppresses aging as defects lead to symptoms seen in aging, bringing about interest in how the protein and hormone work together to fulfill their roles.
Existing on cell surfaces or released from the cell a-Klothos circulates in body fluids including blood. Cell attached form and circulating form of a-Klotho were believed to serve different functions, with the structure and how the protein functions largely unknown until recent.
Combined with recent studies the structure of the protein complex that includes FGF23 and co-receptors challenge widely accepted belief of only attached form of a-Klotho serving as receptor for FGF23 restricting its action to tissues having attached form.
Reflecting a paradigm shift solution for the protein complex structure of circulating form of soluble a-Klotho serving as co-receptor for FGF23 is a possible game changer, soluble form of a-Klotho can go into any cell to act as co-receptor for FGF23 rendering every cell as possible FGF23 target.
Aging, cancer, cardiovascular, neurologic, and kidney disease researchers, as well as patients will benefit from these findings, gained knowledge of protein structure along with molecular binding partners will lead to greater understandings of how a-Klotho works and how to design strategies to block or activate FGF23-A-Klotho interactions and signalling as required.
Evidence of how FGF23 signal cells by forming a complex with a-Klotho and the 2 other molecular partners have been provided by this study, according to the researchers; FGF23 travels via the bloodstream to cells in all organs where it regulates aspects of mineral metabolism, abnormal levels can be found in many disease states, such as chronic kidney disease where high levels are believed to be the cause of many of the complications and fatalities of the disease.
Findings help to highlight how kidney disease leads to abnormal thickening if heart muscle tissues which is a leading cause of death in patients with kidney disease caused by high blood pressure, diabetes, and other diseases; as damaged kidney tubules can no longer eliminate phosphate causing FFG23 to rise initially in effort to keep blood phosphate in check, in time the accumulation can rise to harmful levels. High levels of FGF23 cause hypertrophy, in prevailing hypothesis, being controversial as heart tissue does not have a-Klotho which must be present for FGF23 to signal. Latest findings indicate a-Klotho can be delivered via the bloodstream to organs where not typically present.
Solution for the protein structure will guide future studies, and could launch potential drug development programs, as there are numerous disease that involve a-Klotho deficiency. Replenishment by recombinant protein injections or drugs can have therapeutic implications for cardiovascular, neurologic, kidney, metabolic disease, and cancer.
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