Sandbox Reserved 1653: Difference between revisions

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== Diseases ==

[https://en.wikipedia.org/wiki/Hereditary_stomatocytosis Dehydrated hereditary stomatocytosis] (DHS) is a genetic disease with impaired red blood cell (RBC) membrane properties that affect intracellular cation concentrations.<ref name="Dehydrated"> DOI 10.1038/ncomms2899</ref> The RBCs are abnormally shaped and they result in [https://en.wikipedia.org/wiki/Hemolytic_anemia haemolytic anaemia]. Piezo1 is expressed in the plasma membranes of RBCs, and its role is to control RBCs’ osmolarity. It also plays a prevalent role in the [https://en.wikipedia.org/wiki/Erythropoiesis erythroid differentiation]. Mutations in Piezo1 distort mechanosensitive channel regulation, leading to increased cation transport in erythroid cells.

~~According to studies,~~ Piezo1 ~~mutations are~~ the ~~cause~~ of DHS.<ref name="~~Multiple clinical~~"> DOI 10.~~1182~~/~~blood-2013-02-482489~~</ref> Those mutations could provoke increases in permeability of cations in RBC by different mechanisms. It could induce mechanically activated currents that inactivate more slowly than wild-type currents. They could also affect the inactivation process by either destabilising the inactivated state or stabilising the channel in the open state. As a result, the open to inactivated state equilibrium shifts towards open. Na+ and Ca2+ ion influx consequently increase, and the intracellular K+ concentration decreases in a steady state. The evolution of Piezo1’s function steams from a change in its 3D structure. All the dehydrated hereditary stomatocytosis-associated mutations locate at C-terminal half of Piezo1, but the way it affects Piezo1’s structure is yet to be fully understood.<ref name = "Dehydrated"/>

Because Piezo1 is implicated in the functioning of many cells and organs, modifications on its structure lead to diseases. For instance, Hereditary Xerocytosis (HX) is a rare disease, also called [https://en.wikipedia.org/wiki/Hereditary_stomatocytosis Dehydrated hereditary stomatocytosis] (DHS). This genetic disease leads to impaired red blood cell (RBC) membrane properties that affect intracellular cation concentrations.<ref name="Dehydrated"> DOI 10.1038/ncomms2899</ref> The RBCs are abnormally shaped and they result in [https://en.wikipedia.org/wiki/Hemolytic_anemia haemolytic anaemia]. Those modifications are due to mutations on the FAM38A gene on chromosome 16 which encodes for Piezo 1. Piezo1 is expressed in the plasma membranes of RBCs, and its role is to control RBCs’ osmolarity. It also plays a prevalent role in the [https://en.wikipedia.org/wiki/Erythropoiesis erythroid differentiation]. Mutations in Piezo1 distort mechanosensitive channel regulation, leading to increased cation transport in erythroid cells. Six gain-of-function mutations, gathered in the central core region of the Piezo channel structure, are directly linked to the decrease of inactivation rate of the channel.

Those mutations could provoke increases in permeability of cations in RBC by different mechanisms. It could induce mechanically activated currents that inactivate more slowly than wild-type currents. They could also affect the inactivation process by either destabilising the inactivated state or stabilising the channel in the open state. As a result, the open to inactivated state equilibrium shifts towards open. Na+ and Ca2+ ion influx consequently increase, and the intracellular K+ concentration decreases in a steady state. The evolution of Piezo1’s function steams from a change in its 3D structure.

== Potential therapeutic target ==

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 == Diseases ==
-[https://en.wikipedia.org/wiki/Hereditary_stomatocytosis Dehydrated hereditary stomatocytosis] (DHS) is a genetic disease with impaired red blood cell (RBC) membrane properties that affect intracellular cation concentrations.<ref name="Dehydrated"> DOI 10.1038/ncomms2899</ref> The RBCs are abnormally shaped and they result in [https://en.wikipedia.org/wiki/Hemolytic_anemia haemolytic anaemia]. Piezo1 is expressed in the plasma membranes of RBCs, and its role is to control RBCs’ osmolarity. It also plays a prevalent role in the [https://en.wikipedia.org/wiki/Erythropoiesis erythroid differentiation]. Mutations in Piezo1 distort mechanosensitive channel regulation, leading to increased cation transport in erythroid cells.
-According to studies, Piezo1 mutations are the cause of DHS.<ref name="Multiple clinical"> DOI 10.1182/blood-2013-02-482489</ref> Those mutations could provoke increases in permeability of cations in RBC by different mechanisms. It could induce mechanically activated currents that inactivate more slowly than wild-type currents. They could also affect the inactivation process by either destabilising the inactivated state or stabilising the channel in the open state. As a result, the open to inactivated state equilibrium shifts towards open. Na+ and Ca2+ ion influx consequently increase, and the intracellular K+ concentration decreases in a steady state. The evolution of Piezo1’s function steams from a change in its 3D structure. All the dehydrated hereditary stomatocytosis-associated mutations locate at C-terminal half of Piezo1, but the way it affects Piezo1’s structure is yet to be fully understood.<ref name = "Dehydrated"/>
+Because Piezo1 is implicated in the functioning of many cells and organs, modifications on its structure lead to diseases. For instance, Hereditary Xerocytosis (HX) is a rare disease, also called  [https://en.wikipedia.org/wiki/Hereditary_stomatocytosis Dehydrated hereditary stomatocytosis] (DHS). This genetic disease leads to impaired red blood cell (RBC) membrane properties that affect intracellular cation concentrations.<ref name="Dehydrated"> DOI 10.1038/ncomms2899</ref> The RBCs are abnormally shaped and they result in [https://en.wikipedia.org/wiki/Hemolytic_anemia haemolytic anaemia]. Those modifications are due to mutations on the FAM38A gene on chromosome 16 which encodes for Piezo 1. Piezo1 is expressed in the plasma membranes of RBCs, and its role is to control RBCs’ osmolarity. It also plays a prevalent role in the [https://en.wikipedia.org/wiki/Erythropoiesis erythroid differentiation]. Mutations in Piezo1 distort mechanosensitive channel regulation, leading to increased cation transport in erythroid cells. Six gain-of-function mutations, gathered in the central core region of the Piezo channel structure, are directly linked to the decrease of inactivation rate of the channel.
+Those mutations could provoke increases in permeability of cations in RBC by different mechanisms. It could induce mechanically activated currents that inactivate more slowly than wild-type currents. They could also affect the inactivation process by either destabilising the inactivated state or stabilising the channel in the open state. As a result, the open to inactivated state equilibrium shifts towards open. Na+ and Ca2+ ion influx consequently increase, and the intracellular K+ concentration decreases in a steady state. The evolution of Piezo1’s function steams from a change in its 3D structure.
 == Potential therapeutic target ==