Peroxisomal ether-glycerophospholipid synthesis is dysregulated after TBI.
Journal of Lipid Research,
Год журнала:
2025,
Номер
unknown, С. 100821 - 100821
Опубликована: Май 1, 2025
Ether-glycerophospholipids
(ether-GPs),
the
ether
bond-
(-
O
-)
containing
glycerophospholipids
are
major
components
of
brain
lipidome.
Ether-GPs
play
a
crucial
role
in
regulating
neuronal
function,
and
their
deficiency
has
been
implicated
many
neurodegenerative
diseases.
However,
how
they
affected
after
traumatic
injury
(TBI)
is
not
known.
Our
data
demonstrate
significant
decrease
ether-GPs
abundance
mouse
cortex
following
controlled
cortical
impact
(CCI)
induced
TBI.
This
at
least
part
due
to
impairment
peroxisomal
ether-GP
synthesis
We
detected
dysregulation
synthesizing
enzymes
-
glyceronephosphate-O-acyltransferase
(GNPAT)
alkylglycerone
phosphate
synthase
(AGPS)
injured
brains.
decline
GNPAT
level
fraction
marked
accumulation
AGPS
cytosol
cortices
To
restore
brain,
we
treated
TBI
mice
with
an
precursor
1-O-octadecylglycerol
(OAG)
bypass
steps.
OAG
partially
restored
levels
several
ether-GPs,
attenuated
inflammatory
cytokine
expression
improved
functional
recovery
Taken
together,
our
that
restoration
by
treatment
can
improve
outcomes.
Язык: Английский
Dysregulation of autophagy during photoaging reduce oxidative stress and inflammatory damage caused by UV
Frontiers in Pharmacology,
Год журнала:
2025,
Номер
16
Опубликована: Май 12, 2025
Photoaging,
the
premature
aging
of
skin
due
to
chronic
ultraviolet
(UV)
exposure,
is
a
growing
concern
in
dermatology
and
cosmetic
science.
While
UV
radiation
known
induce
DNA
damage,
oxidative
stress,
inflammation
cells,
recent
research
unveils
promising
countermeasure:
autophagy.
This
review
explores
intricate
relationship
between
autophagy
photoaging,
highlighting
how
this
cellular
recycling
process
can
mitigate
UV-induced
damage.
We
begin
by
examining
differential
impacts
UVA
UVB
on
cells
role
stress
accelerating
photoaging.
Next,
we
delve
into
molecular
mechanisms
autophagy,
including
its
various
forms
regulatory
pathways.
Central
discussion
autophagy's
protective
functions,
such
as
clearance
damaged
organelles
proteins,
maintaining
genomic
integrity.
Furthermore,
address
current
challenges
harnessing
for
therapeutic
purposes,
need
selective
inducers
deeper
understanding
context-dependent
effects.
By
synthesizing
advancements
proposing
future
directions,
underscores
potential
modulation
novel
strategy
prevent
treat
comprehensive
analysis
aims
inspire
further
investigation
autophagy-based
interventions,
offering
new
hope
preserving
health
face
environmental
stressors.
Язык: Английский
Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy
Genes,
Год журнала:
2025,
Номер
16(5), С. 590 - 590
Опубликована: Май 17, 2025
Background:
X-ALD
is
a
white
matter
(WM)
disease
caused
by
mutations
in
the
ABCD1
gene
encoding
transporter
of
very-long-chain
fatty
acids
(VLCFAs)
into
peroxisomes.
Strikingly,
same
mutation
causes
either
devastating
brain
inflammatory
demyelination
during
childhood
or,
more
often,
progressive
spinal
cord
axonopathy
starting
middle-aged
adults.
The
accumulation
undegraded
VLCFA
glial
cell
membranes
and
myelin
has
long
been
thought
to
be
central
mechanism
X-ALD.
Methods:
This
review
discusses
studies
mouse
drosophila
models
that
have
modified
our
views
pathogenesis.
Results:
In
Abcd1
knockout
(KO)
mimics
disease,
late
manifestations
are
rapidly
reversed
transfer
oligodendrocytes
(OLs).
peroxin-5
KO
model,
selective
impairment
peroxisomal
biogenesis
OLs
achieves
an
almost
perfect
phenocopy
cerebral
ALD.
A
model
revealed
myelinating
cells
production
toxic
lipid
able
poison
axons
activate
cells.
Other
showed
critical
role
providing
energy
substrates
axons.
addition,
on
microglial
changing
substates
improved
understanding
neuroinflammation.
Conclusions:
Animal
supporting
primary
axonal
pathology
secondary
microglia
allow
us
revisit
mechanisms.
Beyond
mutations,
pathogenesis
depends
unidentified
contributors,
such
as
genetic
background,
cell-specific
epigenomics,
potential
environmental
triggers,
stochasticity
crosstalk
between
multiple
types
among
billions
neurons.
Язык: Английский
PEX14 acts as the interface linking optineurin to cell type-selective pexophagy
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Май 31, 2024
Abstract
Pexophagy,
the
selective
degradation
of
peroxisomes,
is
essential
for
removing
excess
or
dysfunctional
and
its
dysregulation
linked
to
various
diseases.
Previous
research
has
shown
that
optineurin
(OPTN),
an
autophagy
receptor
involved
in
mitophagy,
aggrephagy,
xenophagy,
can
induce
pexophagy
HEK-293
cells.
However,
underlying
mechanism
remains
unclear.
In
this
study,
we
used
proximity
labeling
identify
PEX14,
a
peroxisomal
membrane
protein,
as
neighboring
partner
OPTN.
Biochemical
analyses
revealed
PEX14
OPTN
interact
through
their
respective
coiled-coil
ubiquitin-binding
domains.
Further
demonstrated
C-terminal
half
overexpressed
triggers
pexophagy,
likely
by
forming
oligomers
with
endogenous
The
co-localization
PEX14-OPTN
complexes
LC3,
combined
suppression
OPTN-mediated
peroxisome
bafilomycin
A1,
supports
model
which
acts
docking
site
on
membrane,
enabling
recruitment
autophagic
machinery
pexophagy.
Summary
This
study
uncovers
defines
protein
key
player
optineurin-driven
advancing
our
mechanistic
understanding
cellular
process.
These
findings
open
new
avenues
developing
therapeutic
strategies
targeting
diseases
associated
defective
Язык: Английский