c-Jun N-terminal kinases (JNKs) are a family of protein
kinases
activated by a myriad of stimuli consequently modulating a vast range
of biological processes. In human postmortem brain samples affected
with Alzheimer′s disease (AD), JNK overactivation has been
described; however, its role in AD onset and progression is still
under debate. One of the earliest affected areas in the pathology
is the entorhinal cortex (EC). Noteworthy, the deterioration of the
projection from EC to hippocampus (Hp) point toward the idea that
the connection between EC and Hp is lost in AD. Thus, the main objective
of the present work is to address if JNK3 overexpression in the EC
could impact on the hippocampus, inducing cognitive deficits. Data
obtained in the present work suggest that JNK3 overexpression in the
EC influences the Hp leading to cognitive impairment. Moreover, proinflammatory
cytokine expression and Tau immunoreactivity were increased both in
the EC and in the Hp. Therefore, activation of inflammatory signaling
and induction of Tau aberrant misfolding caused by JNK3 could be responsible
for the observed cognitive impairment. Altogether, JNK3 overexpression
in the EC may impact on the Hp inducing cognitive dysfunction and
underlie the alterations observed in AD.