Matches in SemOpenAlex for { <https://semopenalex.org/work/W4380853914> ?p ?o ?g. }
- W4380853914 endingPage "23.2023" @default.
- W4380853914 startingPage "ENEURO.0031" @default.
- W4380853914 abstract "Abstract Peripheral administration of tissue inhibitor of metalloproteinases 2 (TIMP2), a protein inhibitor of matrix metalloproteinases (MMPs), has previously been shown to have beneficial effects on cognition and neurons in aged mice. Here, to better understand the potential of recombinant TIMP2 proteins, an IgG4Fc fusion protein (TIMP2-hIgG4) was developed to extend the plasma half-life of TIMP2. Following one month of administration of TIMP2 or TIMP2-hIgG4 via intraperitoneal injections, 23-month-old male C57BL/6J mice showed improved hippocampal-dependent memory in a Y-maze, increased hippocampal cfos gene expression, and increased excitatory synapse density in the CA1 and dentate gyrus (DG) of the hippocampus. Thus, fusion to hIgG4 extended the half-life of TIMP2 while retaining the beneficial cognitive and neuronal effects. Moreover, it retained its ability to cross the blood-brain barrier. To deepen the mechanistic understanding of the beneficial function of TIMP2 on neuronal activity and cognition, a TIMP2 construct lacking MMP inhibitory activity, Ala-TIMP2, was generated, which provides steric hindrance that prevents inhibition of MMPs by the TIMP2 protein while still allowing MMP binding. A comprehensive assessment of the MMP inhibitory and binding capacity of these engineered proteins is outlined. Surprisingly, MMP inhibition by TIMP2 was not essential for its beneficial effects on cognition and neuronal function. These findings both confirm previously published research, expand on the potential mechanism for the beneficial effects of TIMP2, and provide important details for a therapeutic path forward for TIMP2 recombinant proteins in aging-related cognitive decline." @default.
- W4380853914 created "2023-06-16" @default.
- W4380853914 creator A5023663404 @default.
- W4380853914 creator A5024324374 @default.
- W4380853914 creator A5034358740 @default.
- W4380853914 creator A5037456393 @default.
- W4380853914 creator A5053553201 @default.
- W4380853914 creator A5056541582 @default.
- W4380853914 creator A5067102229 @default.
- W4380853914 creator A5074247756 @default.
- W4380853914 creator A5075620744 @default.
- W4380853914 creator A5087314700 @default.
- W4380853914 creator A5092179649 @default.
- W4380853914 date "2023-06-01" @default.
- W4380853914 modified "2023-09-25" @default.
- W4380853914 title "Noncanonical Activity of Tissue Inhibitor of Metalloproteinases 2 (TIMP2) Improves Cognition and Synapse Density in Aging" @default.
- W4380853914 cites W1488124756 @default.
- W4380853914 cites W1513618424 @default.
- W4380853914 cites W1558100964 @default.
- W4380853914 cites W1895946034 @default.
- W4380853914 cites W1914642870 @default.
- W4380853914 cites W1969905245 @default.
- W4380853914 cites W1973838846 @default.
- W4380853914 cites W1978927200 @default.
- W4380853914 cites W1993476760 @default.
- W4380853914 cites W1999845366 @default.
- W4380853914 cites W2007197518 @default.
- W4380853914 cites W2008745393 @default.
- W4380853914 cites W2010233812 @default.
- W4380853914 cites W2014447462 @default.
- W4380853914 cites W2024713762 @default.
- W4380853914 cites W2027329004 @default.
- W4380853914 cites W2030944522 @default.
- W4380853914 cites W2042800560 @default.
- W4380853914 cites W2043335534 @default.
- W4380853914 cites W2047842684 @default.
- W4380853914 cites W2048462242 @default.
- W4380853914 cites W2049989617 @default.
- W4380853914 cites W2062610934 @default.
- W4380853914 cites W2075404997 @default.
- W4380853914 cites W2075593866 @default.
- W4380853914 cites W2081619019 @default.
- W4380853914 cites W2082305527 @default.
- W4380853914 cites W2089813108 @default.
- W4380853914 cites W2091600291 @default.
- W4380853914 cites W2092920470 @default.
- W4380853914 cites W2097971052 @default.
- W4380853914 cites W2101600093 @default.
- W4380853914 cites W2110065044 @default.
- W4380853914 cites W2112239428 @default.
- W4380853914 cites W211436775 @default.
- W4380853914 cites W2124721729 @default.
- W4380853914 cites W2129211163 @default.
- W4380853914 cites W2147915725 @default.
- W4380853914 cites W2150435290 @default.
- W4380853914 cites W2155602568 @default.
- W4380853914 cites W2156735951 @default.
- W4380853914 cites W2157935582 @default.
- W4380853914 cites W2159818315 @default.
- W4380853914 cites W2163179762 @default.
- W4380853914 cites W2231740780 @default.
- W4380853914 cites W2272398100 @default.
- W4380853914 cites W2322201873 @default.
- W4380853914 cites W2331828703 @default.
- W4380853914 cites W2412535695 @default.
- W4380853914 cites W2415013689 @default.
- W4380853914 cites W2606478035 @default.
- W4380853914 cites W2790056846 @default.
- W4380853914 cites W2807960708 @default.
- W4380853914 cites W2884036539 @default.
- W4380853914 cites W2890044737 @default.
- W4380853914 cites W2949501662 @default.
- W4380853914 cites W3133413580 @default.
- W4380853914 cites W3158784430 @default.
- W4380853914 cites W4224301425 @default.
- W4380853914 cites W4313283697 @default.
- W4380853914 cites W4323354665 @default.
- W4380853914 doi "https://doi.org/10.1523/eneuro.0031-23.2023" @default.
- W4380853914 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37321845" @default.
- W4380853914 hasPublicationYear "2023" @default.
- W4380853914 type Work @default.
- W4380853914 citedByCount "1" @default.
- W4380853914 countsByYear W43808539142023 @default.
- W4380853914 crossrefType "journal-article" @default.
- W4380853914 hasAuthorship W4380853914A5023663404 @default.
- W4380853914 hasAuthorship W4380853914A5024324374 @default.
- W4380853914 hasAuthorship W4380853914A5034358740 @default.
- W4380853914 hasAuthorship W4380853914A5037456393 @default.
- W4380853914 hasAuthorship W4380853914A5053553201 @default.
- W4380853914 hasAuthorship W4380853914A5056541582 @default.
- W4380853914 hasAuthorship W4380853914A5067102229 @default.
- W4380853914 hasAuthorship W4380853914A5074247756 @default.
- W4380853914 hasAuthorship W4380853914A5075620744 @default.
- W4380853914 hasAuthorship W4380853914A5087314700 @default.
- W4380853914 hasAuthorship W4380853914A5092179649 @default.
- W4380853914 hasBestOaLocation W43808539141 @default.
- W4380853914 hasConcept C109523444 @default.
- W4380853914 hasConcept C112592302 @default.