COMPOSITIONS AND METHODS USING MATRIX METALLOPROTEINASE (MMP) INHIBITORS FOR TREATING COGNITIVE IMPAIRMENT CHARACTERIZED BY PERSISTENT OR SUSTAINED MMP EXPRESSION AND/OR ACTIVITY

摘要

Particular aspects provide methods for treating cognitive impairment, comprising administration of a therapeutically effective amount of at least one matrix metalloproteinase (MMP) inhibitor sufficient to provide for at least one of precluding, alleviating, reversing, or inhibiting cognitive impairment characterized by sustained elevated expression and/or activity of at least one MMP. Persistent elevations in the expression of MMPs in the hippocampus of aged individuals have a detrimental effect on hippocampal synaptic plasticity, and are an underlying cause of cognitive deficits associated with ageing, and particular aspects therefore provide novel compositions and methods comprising use of MMP (e.g., MMP3 and/or MMP9, etc.) inhibitors to treat age-related cognitive impairment (e.g., cognitive decline). Additional embodiments comprise inhibition of MMP-3 and at least one other MMP (e.g., MMP-9, etc). Exemplary MMP inhibitors comprise a zinc-binding hydroxamate moiety (or a non-hydroxamate zinc-binding moiety), and a peptide or peptidomimetic backbone capable of binding at least one MMP.