Article
Rescue of a lysosomal storage disorder caused by Grn loss of function with a brain penetrant progranulin biologic.
Cell - 2 Sept 2021
Logan Todd, Simon Matthew J, Rana Anil, Cherf Gerald M, Srivastava Ankita, Davis Sonnet S, Low Ray Lieh Yoon, Chiu Chi-Lu, Fang Meng, Huang Fen, Bhalla Akhil, Llapashtica Ceyda, Prorok Rachel, Pizzo Michelle E, Calvert Meredith E K, Sun Elizabeth W, Hsiao-Nakamoto Jennifer, Rajendra Yashas, Lexa Katrina W, Srivastava Devendra B, van Lengerich Bettina, Wang Junhua, Robles-Colmenares Yaneth, Kim Do Jin, Duque Joseph, Lenser Melina, Earr Timothy K, Nguyen Hoang, Chau Roni, Tsogtbaatar Buyankhishig, Ravi Ritesh, Skuja Lukas L, Solanoy Hilda, Rosen Howard J, Boeve Bradley F, Boxer Adam L, Heuer Hilary W, Dennis Mark S, Kariolis Mihalis S, Monroe Kathryn M, Przybyla Laralynne, Sanchez Pascal E, Meisner Rene, Diaz Dolores, Henne Kirk R, Watts Ryan J, Henry Anastasia G, Gunasekaran Kannan, Astarita Giuseppe, Suh Jung H, Lewcock Joseph W, DeVos Sarah L, Di Paolo Gilbert
Abstract excerpt
GRN mutations cause frontotemporal dementia (GRN-FTD) due to deficiency in progranulin (PGRN), a lysosomal and secreted protein with unclear function. Here, we found that Grn-/- mice exhibit a global deficiency in bis(monoacylglycero)phosphate (BMP), an endolysosomal phospholipid we identified as a pH-dependent PGRN interactor as well as a redox-sensitive enhancer of lysosomal proteolysis and lipolysis. Grn-/-...
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