The scientists likewise confirmed that LRRK2 is in a closed, active conformation when it binds to microtubules, which has ramifications for choosing the right kinase inhibitor when treating familial Parkinsons disease.Two types of kinase inhibitors target LRRK2, both of which use different mechanisms to turn off kinase function.- Mark Cookson, National Institute on AgingResearchers are evaluating type 1 inhibitors in medical trials due to the fact that they are more specific and more powerful than type 2 inhibitors.3,4 However, Reck-Petersons structural analysis validates previous findings that some type 1 inhibitors increase LRRK2s microtubule binding.5 This is worrying since LRRK2 can act as an obstruction for molecular motors that move along the microtubules, impeding intracellular trafficking. Her cooperation with Leschziner aims to figure out if LRRK2 kinase inhibitors in fact interrupt this trafficking.Understanding the structure of LRRK2 has important ramifications for familial Parkinsons illness drug design, and has been an ongoing, intricate process for scientists in the field.
As the incidence of Parkinsons illness continues to increase, this disorder positions a big concern on patients, caregivers, and the healthcare system, so therapies that treat its pathology are urgently needed.1,2 While the majority of cases are erratic or idiopathic with no recognized specific cause, Parkinsons illness can be familial, caused by acquiring a mutated gene, such as leucine-rich repeat kinase 2 (LRRK2). Researchers are checking LRRK2-specific kinase inhibitors to treat Parkinsons illness, and an LRRK2-targeted drug just recently advanced into phase III scientific trials.1,3 In a Nature Structural and Molecular Biology paper, Samara Reck-Peterson, a detective and teacher at Howard Hughes Medical Institute, in cooperation with Andres Leschziner at University of California, San Diego, highlights the intricacy of targeting LRRK2 for Parkinsons disease treatment.3 Several researchers formerly examined the structure of LRRK2 and found that this protein can communicate with microtubules.3-5 Using cryo-electron microscopy (cryo-EM), Reck-Petersons team identified the specific LRRK2 amino acids that moderate this interaction. The scientists likewise confirmed that LRRK2 is in a closed, active conformation when it binds to microtubules, which has ramifications for picking the right kinase inhibitor when dealing with familial Parkinsons disease.Two types of kinase inhibitors target LRRK2, both of which utilize different systems to turn off kinase function.- Mark Cookson, National Institute on AgingResearchers are evaluating type 1 inhibitors in scientific trials due to the fact that they are more particular and more potent than type 2 inhibitors.3,4 However, Reck-Petersons structural analysis validates previous findings that some type 1 inhibitors increase LRRK2s microtubule binding.5 This is concerning due to the fact that LRRK2 can act as an obstruction for molecular motors that move along the microtubules, hampering intracellular trafficking. Her partnership with Leschziner aims to figure out if LRRK2 kinase inhibitors really interrupt this trafficking.Understanding the structure of LRRK2 has essential ramifications for familial Parkinsons disease drug design, and has actually been a continuous, complex procedure for researchers in the field.
