L-Lactate Administration Improved Synaptic Plasticity and Cognition in Early 3xTg-AD Mice
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(4), С. 1486 - 1486
Опубликована: Фев. 11, 2025
Synaptic
plasticity
impairment
and
behavioral
deficits
constitute
classical
pathological
hallmarks
in
early-stage
Alzheimer’s
disease
(AD).
Emerging
evidence
suggests
these
synaptic
dysfunctions
may
stem
from
metabolic
dysregulation,
particularly
impaired
aerobic
glycolysis.
As
a
key
product
of
astrocyte-mediated
glycolysis,
lactate
serves
dual
roles
as
both
an
energy
substrate
signaling
molecule,
playing
critical
regulatory
role
long-term
memory
formation.
This
study
investigated
whether
exogenous
L-lactate
supplementation
could
ameliorate
dysfunction
cognitive
AD
models.
Our
findings
reveal
significant
reductions
hippocampal
levels
experimental
mice.
Systemic
administration
(200
mg/kg)
effectively
restored
physiological
concentrations
tissue
cerebrospinal
fluid
(CSF).
Chronic
treatment
significantly
improved
spatial
learning
performance
assessments.
Electrophysiological
recordings
demonstrated
that
either
acute
bath
application
(2
mM)
to
slices
or
chronic
intraperitoneal
enhanced
high-frequency
stimulation
(HFS)-induced
potentiation
(LTP)
magnitude
3xTg-AD
Ultrastructural
analysis
revealed
density
morphological
features
synapses.
At
the
molecular
level,
upregulated
marker
synaptophysin
(SYP)
expression
while
downregulating
activity-regulated
cytoskeletal-associated
protein
(ARC)
These
multimodal
demonstrate
restores
function
mice
through
concurrent
improvements
at
behavioral,
structural,
levels.
Язык: Английский
Lactylation: A Novel Epigenetic Regulator of Cellular Senescence
Aging and Disease,
Год журнала:
2025,
Номер
unknown, С. 0 - 0
Опубликована: Янв. 1, 2025
Cellular
senescence
is
the
basic
unit
of
organismal
aging,
a
complicated
biological
process
involving
several
cell
types
and
tissues.
It
also
an
important
mechanism
by
which
body
responds
to
damage
potential
carcinogenesis.
However,
excessive
or
abnormal
cellular
can
lead
tissue
functional
degradation
occurrence
diseases.
In
recent
years,
role
epigenetic
modifications
in
has
received
extensive
attention.
Lactylation,
novel
post-translational
modification
derived
from
lactate,
recently
gained
significant
attention
as
key
factor
metabolism
regulation,
gradually
demonstrating
its
importance
regulation
senescence.
This
review
emphasizes
bidirectional
causal
relationship
between
lactylation
senescence,
highlighting
therapeutic
target
for
aging-related
Язык: Английский
Lactylation in CNS disorders: mechanisms, cellular function, and disease relevance
Frontiers in Cell and Developmental Biology,
Год журнала:
2025,
Номер
13
Опубликована: Март 28, 2025
Lactate,
as
a
metabolic
product
or
energy
substrate,
participates
in
various
neurological
processes
within
the
physiological
and
pathological
frameworks
of
central
nervous
system
(CNS).
The
groundbreaking
application
multi-omics
integration
technologies
has
unveiled
novel
role
for
lactate:
lactylation,
unique
post-translational
modification
(PTM)
that
covalently
attaches
lactate
groups
to
lysine
residues
on
proteins.
This
process
precisely
regulates
protein
function
gene
expression,
profoundly
influencing
progression
diseases.
lactylation
is
meticulously
regulated
by
variety
key
enzymes
pathways,
forming
dynamic
intricate
network.
In
this
review,
we
summarize
involved
specifically
"Writers,"
"Erasers,"
"Readers."
Furthermore,
systematically
categorize
observed
cell
types
CNS
investigate
its
multifaceted
roles
processes,
including
neurodegenerative
diseases,
brain
tumors,
injuries.
By
consolidating
latest
research
findings
field,
our
review
aims
highlight
significance
these
discoveries
future
explore
their
potential
translational
applications.
Язык: Английский
UGDH Lactylation Aggravates Osteoarthritis by Suppressing Glycosaminoglycan Synthesis and Orchestrating Nucleocytoplasmic Transport to Activate MAPK Signaling
Advanced Science,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 27, 2025
Osteoarthritis
(OA)
progression
is
closely
related
to
dysregulated
glycolysis.
As
the
primary
metabolite
of
glycolysis,
lactate
plays
a
detrimental
role
in
OA.
However,
how
exacerbates
OA
process
remains
unclear.
Here,
this
study
revealed
that
levels
are
elevated
synovial
fluid
patients
and
IL-1β-treated
human
chondrocytes,
promoting
protein
pan-lactylation.
Functionally,
hyper-lactylation
chondrocytes
extracellular
matrix
(ECM)
degradation
cell
apoptosis
vitro
vivo.
Moreover,
UDP-glucose
dehydrogenase
(UGDH)
proven
be
key
lactylated
lactate-treated
which
undergoes
lactylation
at
lysine
6
(K6).
Lactylated
UGDH
repressed
its
enzymatic
activity,
reducing
glycosaminoglycan
synthesis
disregulating
nuclear-cytoplasmic
distribution.
Mechanistically,
K6
impedes
interaction
signal
transducer
activator
transcription
1
(STAT1),
thus
mitogen-activated
kinase
8
(MAP3K8)
activating
MAPK
signaling
pathway.
Importantly,
vivo
treatment
with
A485,
specific
acyltransferase
P300
inhibitor,
suppressed
rescued
ECM
progression.
These
findings
uncover
new
mechanism
underlying
pathogenesis
highlight
potential
targeting
as
novel
therapeutic
strategy
for
Язык: Английский
Glucose oxidase-embedded mesoporous polydopamine nanoparticles produce CO for synergistic tumor starvation, chemodynamic, and photothermal therapy
Colloids and Surfaces B Biointerfaces,
Год журнала:
2025,
Номер
253, С. 114729 - 114729
Опубликована: Апрель 23, 2025
Язык: Английский
GBE1 alleviates MPTP-induced PD symptoms in mice by enhancing glycolysis and oxidative phosphorylation
Brain Research,
Год журнала:
2025,
Номер
unknown, С. 149663 - 149663
Опубликована: Апрель 1, 2025
Язык: Английский
Lactate links exercise to synaptic protection and cognitive enhancement in Alzheimer’s disease models
BMC Medicine,
Год журнала:
2025,
Номер
23(1)
Опубликована: Июнь 3, 2025
Physical
exercise
is
known
to
promote
cognitive
resilience
in
aging
and
Alzheimer's
disease
(AD),
but
the
underlying
mechanisms
remain
incompletely
understood.
Lactate,
a
metabolic
byproduct
elevated
during
exercise,
has
recently
emerged
as
potential
neuromodulator
of
brain
function.
Three
AD-like
mouse
models
(SAMP8,
Aβ1-42
injection,
5xFAD)
were
used
evaluate
effects
treadmill
on
function
synaptic
plasticity.
Serum
lactate
levels
assessed,
sodium
L-lactate
(NaLA)
was
administered
determine
its
neuroprotective
effects.
Transcriptomic
analysis
performed
hippocampal
tissue
explore
lactate-regulated
pathways.
Lactate
transport
pharmacologically
inhibited
using
4-CIN
for
mechanistic
validation.
Treadmill
significantly
improved
performance
increased
synapse-associated
protein
expression
AD
models.
Exercise
serum
levels,
exogenous
NaLA
administration
recapitulated
benefits
exercise.
profiling
revealed
enrichment
genes
involved
axon
guidance
organization,
including
upregulation
multiple
Eph
receptor
family
genes.
α-cyano-4-hydroxycinnamic
acid
(4-CIN)
abolished
exercise-induced
effects,
confirming
essential
role
mediating
these
benefits.
This
study
identifies
critical
mediator
linking
enhanced
improvement
models,
providing
insights
highlighting
metabolism
therapeutic
target
AD.
Язык: Английский
Lactylation of tau in human Alzheimer's disease brains
Xiaoyu Zhang,
Yan Liu,
Michaella J. Rekowski
и другие.
Alzheimer s & Dementia,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 30, 2024
Aggregation
of
hyperphosphorylated
tau
(tauopathy)
is
associated
with
cognitive
impairment
in
patients
Alzheimer's
disease
(AD).
In
AD,
a
metabolic
shift
due
to
the
Warburg
effect
results
increased
lactate
production.
Lactate
can
induce
post-translational
modification
(PTM)
on
proteins
that
conjugates
lactyl
groups
lysine
(K)
residues,
which
known
as
lactylation.
Язык: Английский
Chronic mitochondrial fragmentation elicits a neuroprotective Warburg-like effect in Drosophila neurons
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 1, 2024
Abstract
Mitochondrial
fission
and
fusion
are
dynamic
important
cellular
processes,
but
the
roles
of
these
two
very
different
mitochondrial
forms
–
predominantly
spherical
tubular
-
not
well-characterized
in
neurons
animals
especially
aging
neurons.
This
is
because
long-lived
dynamics
associated
with
neurodegenerative
diseases.
We
used
here
an
efficient
cell
type-specific
CRISPR
approach
to
knockout
key
fission-fusion
genes
disrupt
within
inessential
clock
Drosophila
.
Surprisingly,
much
more
than
for
maintaining
long-term
neuronal
function.
Neurons
survive
chronic
fragmentation
due
loss
by
triggering
a
cancer-like
transcriptomic
response.
Warburg
effect
includes
ATF4-mediated
upregulation
aerobic
glycolysis
gene
Lactate
dehydrogenase
(
Ldh
),
LDH
essential
prevent
neurodegeneration
deficient
Opa1
These
results
others
provide
insights
into
intersection
metabolism,
neurodegeneration.
Язык: Английский