The abnormal phosphorylation of the τ-protein is
a typical
early pathological feature of Alzheimer’s disease (AD). The
excessive phosphorylation of the τ-protein in the brain causes
the formation of neurofibrillary tangles (NFTs) and increases the
neurotoxicity of amyloid-β (Aβ). Thus, targeting the τ-protein
is considered a promising strategy for treating AD. Herein, we designed
and synthesized a series of molecules containing bifunctional groups
to recognize the τ-protein and the E3 ligase. The molecules
were examined
in vitro
, and their effects were tested
on PC12 cells. In addition, we further studied the pharmacokinetics
of compound I3 in healthy rats. Our data showed that compound I3 could
effectively degrade τ-protein, reduce Aβ-induced cytotoxicity,
and regulate the uneven distribution of mitochondria, which may open
a new therapeutic strategy for the treatment of AD.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.