ML-SA1 explained

ML-SA1 is a chemical compound which acts as an "agonist" (i.e. channel opener) of the TRPML family of calcium channels. It has mainly been studied for its role in activating TRPML1 channels, although it also shows activity at the less studied TRPML2 and TRPML3 subtypes. TRPML1 is important for the function of lysosomes, and ML-SA1 has been used to study several disorders resulting from impaired lysosome function, including mucolipidosis type IV and Niemann-Pick's disease type C,[1] [2] [3] [4] as well as other conditions such as stroke and Alzheimer's disease.[5] [6]

Notes and References

  1. Feng X, Xiong J, Lu Y, Xia X, Zhu MX . Differential mechanisms of action of the mucolipin synthetic agonist, ML-SA1, on insect TRPML and mammalian TRPML1 . Cell Calcium . 56 . 6 . 446–56 . December 2014 . 25266962 . 10.1016/j.ceca.2014.09.004 . 4252876 .
  2. Erkhembaatar M, Gu DR, Lee SH, Yang YM, Park S, Muallem S, Shin DM, Kim MS . 6 . 2+ Signaling is Essential for Osteoclastogenesis and Bone Remodeling . Journal of Bone and Mineral Research . 32 . 2 . 385–396 . February 2017 . 27589205 . 10.1002/jbmr.2986 . 9850942 .
  3. Gómez NM, Lu W, Lim JC, Kiselyov K, Campagno KE, Grishchuk Y, Slaugenhaupt SA, Pfeffer BA, Fliesler SJ, Mitchell CH . 6 . Robust lysosomal calcium signaling through channel TRPML1 is impaired by lysosomal lipid accumulation . FASEB Journal . 32 . 2 . 782–794 . February 2018 . 29030399 . 10.1096/fj.201700220RR . free . 5888396 .
  4. Fine M, Schmiege P, Li X . 2-mediated human TRPML1 regulation . Nature Communications . 9 . 1 . 4192 . October 2018 . 30305615 . 10.1038/s41467-018-06493-7 . free . 6180102 .
  5. Wang Y, Jiang SW, Liu X, Niu L, Ge XL, Zhang JC, Wang HR, Fei AH, Gao CJ, Pan SM . 6 . Degradation of TRPML1 in Neurons Reduces Neuron Survival in Transient Global Cerebral Ischemia . Oxidative Medicine and Cellular Longevity . 2018 . 2018 . 4612727 . 30662583 . 10.1155/2018/4612727 . free . 6312622 .
  6. Hui L, Soliman ML, Geiger NH, Miller NM, Afghah Z, Lakpa KL, Chen X, Geiger JD . 6 . Acidifying Endolysosomes Prevented Low-Density Lipoprotein-Induced Amyloidogenesis . Journal of Alzheimer's Disease . 2019 . 67 . 1 . 393–410 . 30594929 . 10.3233/JAD-180941 . 6425476 .

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