Amyloid pathology triggered in vitro drives the heterodimerization of transcription factors CREB3L2 and ATF4
In a collaborative effort between the Laboratory of Local Translation in Neurons and Glia and the Taub Institute for Research on Alzheimer´s Disease and the Aging Brain (Hengst lab) researchers have found that amyloid pathology triggered in vitro drives the heterodimerization of transcription factors CREB3L2 and ATF4.
CREB3L2-ATF4 dimer formation is enhanced in Alzheimer´s disease (AD) mouse models and in brain tissues from AD patients. Interestingly, CREB3L2-ATF4 dimers dysregulate retromer functio, APP processing and promote Tau hyperphosphorylation, all hallmarks of AD. CREB3L2-ATF4-dependent transcriptional programs can be targeted by the antitumoral drug dovitinib, making signaling downstream of CREB3L2-ATF4 heterodimers amenable to therapeutic intervention.
This work led by Dr. Claúdio Goveia Roque has been recently published in Science Advances.
CREB3L2-ATF4 dimers in the prefrontal cortex of an AD patient (green). Neurons are stained in magenta.