pr-957 and Alzheimer-Disease

The immunoproteasome (iP), an inducible proteasome variant harboring three immunosubunits, low molecular mass polypeptide-2 (LMP2), multicatalytic endopeptidase complex subunit-1, and low molecular mass polypeptide-7 (LMP7), is involved in multiple facets of inflammatory responses. We recently reported that YU102, a dual inhibitor of the iP subunit LMP2 and the constitutive proteasome catalytic subunit β1, ameliorates cognitive impairments in mouse models of Alzheimer's disease (AD) independently of amyloid deposits. To investigate whether inhibition of LMP2 is sufficient to improve the cognitive functions of AD mice, here we prepared 37 YU102 analogues and identified a potent LMP2 inhibitor DB-310 (

Topics: Alzheimer Disease; Animals; Cell Line, Transformed; Cysteine Endopeptidases; Cysteine Proteinase Inhibitors; Epithelial-Mesenchymal Transition; Humans; Interleukin-1alpha; Mice, Transgenic; Microglia; Molecular Structure; Nootropic Agents; Oligopeptides; Small Molecule Libraries; Structure-Activity Relationship