Microorganisms,
Год журнала:
2024,
Номер
12(6), С. 1133 - 1133
Опубликована: Июнь 1, 2024
Simvastatin,
a
blockbuster
drug
for
treating
hypercholesterolemia,
has
multifactorial
benefits
as
an
antimicrobial
agent
and
plays
preventative
role
in
reducing
the
incidence
of
Alzheimer’s
Disease
(AD).
Although
most
beneficial
effects
simvastatin
have
been
attributed
to
its
ability
reduce
cholesterol
levels,
recent
scientific
studies
suggested
that
are
largely
due
pleiotropic
targeting
other
pathways,
e.g.,
by
inhibiting
protein
lipidation.
There
certain
can
be
predicted
from
inhibition
mevalonate
pathway;
however,
some
proteostasis
lead
reduced
levels
amyloid
beta,
key
contributor
AD.
This
review
discusses
use
anti-AD
drug.
Research Square (Research Square),
Год журнала:
2025,
Номер
unknown
Опубликована: Март 25, 2025
Abstract
Phosphorylation
targeting
chimeras
(PhosTACs)
recruit
phosphatases
to
dephosphorylate
target
proteins
by
proximity-induced
protein
interactions.
However,
recruiting
a
phosphatase
subunit
or
holoenzyme
using
small
molecules
without
compromising
its
activity
adversely
disturbing
cellular
function
remains
challenging.
In
addition,
many
do
not
have
favorable
activator
binder
currently.
To
overcome
these
limitations,
here,
we
report
an
adapted
mode
of
action,
named
togoPhosTAC,
based
on
the
molecule
PhosTAC,
engineered
fusion
FKBP12(F36V)-phosphatase,
and
lipid-based
delivery
system
for
targeted
dephosphorylation.
Through
nanoparticles,
delivered
pre-fused
complex
PhosTACs
FKBP12(F36V)-phosphatases
in
mRNA
format
directly
rapid
efficient
intracellular
The
togoPhosTAC
was
able
epidermal
growth
factor
receptor
(EGFR),
tau,
α-synuclein.
Furthermore,
togoPhosTAC-mediated
tau
dephosphorylation
also
correlates
with
reduced
aggregation.
sum,
our
hybrid
biologic
adaptor
strategy
bypassed
challenges
ligand
development
provided
alternative
generalizable
solution
precise
modulation
in
cellulo.
Brain Research Bulletin,
Год журнала:
2025,
Номер
unknown, С. 111321 - 111321
Опубликована: Март 1, 2025
The
dysregulation
of
cholesterol
metabolism
homeostasis
has
been
universally
suggested
in
the
aeotiology
Alzheimer's
disease
(AD).
Initially,
studies
indicate
that
alteration
serum
level
might
contribute
to
AD.
However,
because
blood-brain
barrier
impedes
entry
plasma
cholesterol,
brain
cells
are
not
directly
influenced
by
cholesterol.
Furthermore,
mounting
evidences
suggest
a
link
between
and
Interestingly,
Amyloid-β
proteins
(Aβ)
can
markedly
inhibit
cellular
biosynthesis
lower
content
cultured
cells.
And
Aβ
overproduction/overload
induces
significant
decrease
familial
AD
(FAD)
animals.
Importantly,
mutations
or
polymorphisms
genes
related
transportation,
such
as
ApoE4,
ATP
binding
cassette
(ABC)
transporters,
low-density
lipoprotein
receptor
(LDLR)
family
Niemann-Pick
C
1
2
(NPC1/2),
obviously
lead
decreased
transport,
resulting
loss,
which
could
be
tightly
associated
with
pathological
impairments.
Additionally,
accumulating
data
show
there
reduction
and/or
disorder
trafficking
variety
sporadic
(SAD)
animals
patients.
Collectively,
compelling
FAD
SAD
share
one
common
overlapping
neurochemical
mechanism:
neuronal/cellular
deficiency.
Therefore,
accumulated
strongly
support
novel
hypothesis
deficiency
contributes
onset
progression
This
review
highlights
pivotal
role
pathogenesis
offers
valuable
insights
for
future
development
treatment.
Frontiers in Aging Neuroscience,
Год журнала:
2023,
Номер
15
Опубликована: Окт. 19, 2023
Alzheimer’s
disease
(AD)
is
the
primary
cause
of
dementia
and
anticipated
to
impose
a
substantial
economic
burden
in
future.
Over
significant
period,
widely
accepted
amyloid
cascade
hypothesis
has
guided
research
efforts,
recent
FDA
approval
an
anti-
amyloid-beta
(Aβ)
protofibrils
antibody,
believed
decelerate
AD
progression,
further
solidified
its
significance.
However,
excessive
emphasis
placed
on
overshadowed
physiological
nature
Aβ
tau
proteins
within
axons.
Axons,
specialized
neuronal
structures,
sustain
damage
during
early
stages
AD,
exerting
pivotal
influence
progression.
In
this
review,
we
present
comprehensive
summary
relationship
between
axonal
pathology,
amalgamating
roles
proteins,
along
with
impact
risk
genes
such
as
APOE
TREM2.
Furthermore,
underscore
exceptional
significance
context
AD.
Antioxidants and Redox Signaling,
Год журнала:
2024,
Номер
unknown
Опубликована: Июнь 6, 2024
Cholesterol
plays
a
crucial
role
in
the
brain,
where
it
is
highly
concentrated
and
tightly
regulated
to
support
normal
brain
functions.
It
serves
as
vital
component
of
cell
membranes,
ensuring
their
integrity,
acts
key
regulator
various
processes.
Dysregulation
cholesterol
metabolism
has
been
linked
impaired
function
onset
neurodegenerative
diseases
such
Alzheimer's
disease
(AD),
Parkinson's
disease,
Huntington's
disease.
Microorganisms,
Год журнала:
2024,
Номер
12(6), С. 1133 - 1133
Опубликована: Июнь 1, 2024
Simvastatin,
a
blockbuster
drug
for
treating
hypercholesterolemia,
has
multifactorial
benefits
as
an
antimicrobial
agent
and
plays
preventative
role
in
reducing
the
incidence
of
Alzheimer’s
Disease
(AD).
Although
most
beneficial
effects
simvastatin
have
been
attributed
to
its
ability
reduce
cholesterol
levels,
recent
scientific
studies
suggested
that
are
largely
due
pleiotropic
targeting
other
pathways,
e.g.,
by
inhibiting
protein
lipidation.
There
certain
can
be
predicted
from
inhibition
mevalonate
pathway;
however,
some
proteostasis
lead
reduced
levels
amyloid
beta,
key
contributor
AD.
This
review
discusses
use
anti-AD
drug.
