Tau degradation in Alzheimer's disease: Mechanisms and therapeutic opportunities
Alzheimer s & Dementia,
Journal Year:
2025,
Volume and Issue:
21(3)
Published: March 1, 2025
Abstract
In
Alzheimer's
disease
(AD),
tau
undergoes
abnormal
post‐translational
modifications
and
aggregations.
Impaired
intracellular
degradation
pathways
further
exacerbate
the
accumulation
of
pathological
tau.
A
new
strategy
–
targeted
protein
recently
emerged
as
a
modality
in
drug
discovery
where
bifunctional
molecules
bring
target
close
to
machinery
promote
clearance.
Since
2016,
this
has
been
applied
pathologies
attracted
broad
interest
academia
pharmaceutical
industry.
However,
systematic
review
recent
studies
on
mechanisms
is
lacking.
Here
we
(the
ubiquitin–proteasome
system
autophagy–lysosome
pathway),
their
dysfunction
AD,
tau‐targeted
degraders,
such
proteolysis‐targeting
chimeras
autophagy‐targeting
chimeras.
We
emphasize
need
for
continuous
exploration
provide
future
perspective
developing
encouraging
researchers
work
treatment
options
AD
patients.
Highlights
Post‐translational
modifications,
aggregation,
mutations
affect
degradation.
vicious
circle
exists
between
impaired
pathologies.
Ubiquitin
plays
an
important
role
complex
pathways.
Tau‐targeted
degraders
promising
strategies
novel
treatment.
Language: Английский
Development of PROTACs targeting estrogen receptor: An emerging technique for combating endocrine resistance
RSC Medicinal Chemistry,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Dec. 30, 2024
ER
PROTACs
emerge
as
a
hopeful
and
innovative
strategy
for
combating
endocrine-resistant
breast
cancer.
Language: Английский