BAG-1M co-activates BACE1 transcription through NF- κB and accelerates Aβ production and memory deficit in Alzheimer’s disease mouse model

In this report, we found that over-expression of BAG-1M enhances BACE1-mediated cleavage of amyloid precursor protein (APP) and Aβ production by up-regulating BACE1 gene transcription. The regulation of BACE1 transcription by BAG-1M was dependent on NF-κB, as BAG-1M complexes NF-κB at the promoter of BACE1 gene and co-activates NF-κB-facilitated BACE1 transcription. Moreover, expression of BAG-1M by lentiviral vector in the hippocampus of AD transgenic model mice promotes Aβ generation and formation of neuritic plaque, and subsequently accelerates memory deficits of the mice. These results provide evidence for an emerging role of BAG-1M in the regulation of BACE1 expression and AD pathogenesis and that targeting the BAG-1M-NF-κB complex may provide a mechanism for inhibiting Aβ production and plaque formation.
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research