biostudies-literatureUnknown39(10)Keller MThe metalloprotease meprin β is known for its multifunctional involvement in various physiological processes throughout the body including the brain. However, its broader functions within the brain besides amyloid β generation remain largely unexplored. To investigate this, we utilized a mouse model overexpressing meprin β in neurons within the cortex and hippocampus, regions crucial for learning and memory. Behavioral assessments, employing the Morris' Water Maze paradigm test, revealed impaired cognitive functions in animals overexpressing meprin β. Furthermore, electrophysiological recordings in hippocampal slices using multielectrode arrays showed an impaired long-term potentiation (LTP) in meprin β-overexpressing mice compared to wild-type counterparts. Intriguingly, concomitant with FASEB journal : official publication of the Federation of American Societies for Experimental Biologye70616https://www.ebi.ac.uk/biostudies/studies/S-EPMC12093287biostudies-literatureMeprin β Modulates Brevican Proteolysis Impairing Neural Plasticity and Memory Formation.PMC12093287Tholey AKreiselmaier SBecker-Pauly CSchmitt UBickenbach KMittmann TPietrzik CUKeller MMarengo LTaghikhah DAbukhalaf MGallagher CfalseMeprin β Modulates Brevican Proteolysis Impairing Neural Plasticity and Memory Formation.The metalloprotease meprin β is known for its multifunctional involvement in various physiological processes throughout the body including the brain. However, its broader functions within the brain besides amyloid β generation remain largely unexplored. To investigate this, we utilized a mouse model overexpressing meprin β in neurons within the cortex and hippocampus, regions crucial for learning and memory. Behavioral assessments, employing the Morris' Water Maze paradigm test, revealed impaired cognitive functions in animals overexpressing meprin β. Furthermore, electrophysiological recordings in hippocampal slices using multielectrode arrays showed an impaired long-term potentiation (LTP) in meprin β-overexpressing mice compared to wild-type counterparts. Intriguingly, concomitant with 2025-01-01T00:00:00Z2025 May2026-06-01T05:21:17.478Z2026-04-08T09:31:08.559ZS-EPMC120932874039634610.1096/fj.202500017R