UNASSIGNED: MicroRNAs (miRNAs) that regulate mRNA stability have been linked to amyloid production, tau phosphorylation, and @entity32 in @entity195 ( @entity195 ). However, whether cerebral miRNA networks are dysregulated during the earliest stages of @entity195 remains underexplored. We performed miRNA expression analysis using frontal cortex tissue harvested from subjects who died with a clinical diagnosis of no @entity73 (NCI), @entity73 ( @entity73 , a putative prodromal @entity195 stage), or mild @entity195 . Analysis revealed that the miRNA clusters @entity31611 /132 and @entity21176 /23b were down-regulated in the frontal cortex of @entity73 subjects. Both @entity31611 /132 and @entity21176 /b are predicted to destabilize the message for @entity4093 ( @entity4093 ); hence, down-regulation of either @entity31611 /132 or @entity21176 /b in frontal cortex should promote @entity4093 mRNA expression in this region. qPCR studies revealed that frontal cortex levels of @entity4093 were increased in @entity73 . Given the ability of frontal cortex to respond to the onset of @entity303 by neuronal reorganization, these data suggest that miRNA-mediated up-regulation of the @entity4093 pathway represents a compensatory response to the onset of the disease. By contrast, qPCR analysis of inferior temporal cortex, an area affected early in the progression of @entity195 , showed no changes in @entity31611 /132, @entity21176 /b, or @entity4093 transcripts in the same @entity73 subjects. In vitro mechanistic studies showed that coordinated down-regulation of @entity31611 and @entity21176 increased @entity4093 protein expression and provided neuroprotection from b-amyloid @entity137 in @entity1 neuronal cells. Taken together, these data suggest a novel miRNA-mediated neuroprotective pathway activated during the progression of @entity195 that may be amenable to therapeutic manipulation.

Evidence for a neuroprotective microRNA pathway in XXXX .

@entity1 :: ('9606', 'Species') :: ['human'] @entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity31611 :: ('406994', 'Gene') :: ['miR-212'] @entity4093 :: ('23411', 'Gene') :: ['sirtuin 1', 'sirt1'] @entity73 :: ('MESH:D003072', 'Disease') :: ['cognitive impairment', 'amnestic mild cognitive impairment', 'aMCI'] @entity21176 :: ('407010', 'Gene') :: ['miR-23a', 'miR23a'] @entity303 :: ('MESH:D003704', 'Disease') :: ['dementia'] @entity195 :: ('MESH:D000544', 'Disease') :: ['AD', "Alzheimer's disease"]
@entity73 :: (MESH:D003072,Disease) :: ['amnestic mild cognitive impairment']
