Apolipoprotein E in Alzheimer’s disease: molecular insights and therapeutic opportunities
Molecular Neurodegeneration,
Год журнала:
2025,
Номер
20(1)
Опубликована: Апрель 24, 2025
Abstract
Apolipoprotein
E
(
APOE-
gene;
apoE-
protein)
is
the
strongest
genetic
modulator
of
late-onset
Alzheimer’s
disease
(AD),
with
its
three
major
isoforms
conferring
risk
for
ε2
<
ε3
ε4.
Emerging
protective
gene
variants,
such
as
APOE
Christchurch
and
COLBOS
variant
REELIN
,
an
alternative
target
certain
apoE
receptors,
offer
novel
insights
into
resilience
against
AD.
In
recent
years,
role
has
been
shown
to
extend
beyond
primary
function
in
lipid
transport,
influencing
multiple
biological
processes,
including
amyloid-β
(Aβ)
aggregation,
tau
pathology,
neuroinflammation,
autophagy,
cerebrovascular
integrity
protection
from
peroxidation
resulting
ferroptotic
cell
death.
While
detrimental
influence
ε4
on
these
other
processes
well
described,
molecular
mechanisms
underpinning
this
disadvantage
require
further
enunciation,
particularly
realize
therapeutic
opportunities
related
apoE.
This
review
explores
multifaceted
roles
AD
pathogenesis,
emphasizing
discoveries
translational
approaches
apoE-mediated
pathways.
These
findings
underscore
potential
apoE-based
strategies
prevent
or
mitigate
genetically
at-risk
populations.
Язык: Английский
The metabolic underpinnings of sebaceous lipogenesis
Communications Biology,
Год журнала:
2025,
Номер
8(1)
Опубликована: Апрель 27, 2025
Abstract
Sebaceous
glands
synthesize
and
secrete
sebum,
a
mélange
of
lipids
other
cellular
products
that
safeguards
the
mammalian
integument.
Differentiating
sebocytes
delaminate
from
basal
membrane
dislodge
towards
gland’s
middle,
where
they
eventually
undergo
poorly
understood
death
mode
in
which
whole
cell
becomes
secretion
product
(holocrine
secretion).
Supported
by
recent
transcriptomics
data,
this
review
examines
idea
peripheral
have
remarkable
ability
to
draw
nutrients
blood
become
committed
unrestrainedly
invest
all
available
resources
into
synthetic
processes
for
accomplishing
sebum
synthesis,
thereby
exploiting
core
metabolic
fluxes
as
glycogen
turnover,
glutamine-directed
anaplerosis,
pentose
phosphate
pathway
de
novo
lipogenesis.
Finally,
we
propose
metabolic-driven
are
an
important
mechanistic
component
holocrine
secretion.
A
deeper
understanding
these
adaptations
could
indicate
novel
strategies
modulating
key
pathogenic
factor
acne
skin
diseases.
Язык: Английский
Rewiring lipid metabolism to enhance immunotherapy efficacy in melanoma: a frontier in cancer treatment
Frontiers in Oncology,
Год журнала:
2025,
Номер
15
Опубликована: Май 1, 2025
Immunotherapy
has
transformed
the
landscape
of
melanoma
treatment,
offering
significant
extensions
in
survival
for
many
patients.
Despite
these
advancements,
nearly
50%
cases
remain
resistant
to
such
therapies,
highlighting
need
novel
approaches.
Emerging
research
identified
lipid
metabolism
reprogramming
as
a
key
factor
promoting
progression
and
resistance
immunotherapy.
This
not
only
supports
tumor
growth
metastasis
but
also
creates
an
immunosuppressive
environment
that
impairs
effectiveness
treatments
immune
checkpoint
inhibitors
(ICIs).
review
delves
into
intricate
relationship
between
system
interactions
melanoma.
We
will
explore
how
alterations
metabolic
pathways
contribute
evasion
therapy
resistance,
emphasizing
recent
discoveries
this
area.
Additionally,
we
highlights
therapeutic
strategies
targeting
enhance
inhibitor
(ICI)
efficacy.
Язык: Английский
Corneal Mucin‐Targeting Liposome Nanoplatforms Enable Effective Treatment of Dry Eye Diseases by Integrated Regulation of Ferroptosis and Inflammation
Advanced Science,
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 28, 2024
Abstract
The
incidence
of
dry
eye
disease
(DED)
has
been
increasing
annually
worldwide,
creating
an
urgent
need
for
new
therapies.
Due
to
the
multifactorial
mechanism
underlying
DED,
traditional
medications
focused
on
decreasing
ocular
surface
inflammation
have
unable
address
all
harmful
factors
and
fail
achieve
a
complete
clinical
cure.
Ferroptosis,
form
programmed
cell
death
characterized
by
lipid
peroxidation,
become
pivotal
contributor
oxidative
stress‐driven
pathology.
Therefore,
therapeutic
targeting
ferroptosis
may
be
attractive
option
management.
Herein,
sialic
acid‐targeting
peptide‐modified
liposome
loaded
with
Cyclosporine
A
(CsA),
typical
anti‐inflammatory
drug,
Ferrostatin‐1
(Fer‐1),
selective
inhibitor,
is
developed
termed
as
CF@SNPs,
combing
sustaining
DED
treatment.
This
multifunctional
liposomal
encapsulation
demonstrates
excellent
aqueous
solubility;
moreover,
peptide
prolongs
retention,
further
enhancing
efficacy.
CF@SNPs
treatment
comprehensively
alleviates
symptoms,
including
improving
corneal
defects,
augmenting
goblet
count,
restoring
tear
secretion.
Specifically,
attenuate
pathology
suppressing
p53‐SLC7A11‐GSH‐dependent
TNF‐α‐associated
inflammatory
cascades,
accompanied
favorable
biocompatibility
in
vivo.
These
results
underscore
promising
potential
this
superior
nano‐formulation
pharmacotherapy.
Язык: Английский