Immunological Reviews,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 23, 2024
Summary
Alzheimer's
disease
(AD)
is
the
most
common
neurodegenerative
disorder
and
cause
of
dementia.
Despite
prevalence
AD,
there
a
lack
effective
modifying
therapies.
Recent
evidence
indicates
that
gut
microbiome
(GMB)
may
play
role
in
AD
through
its
regulation
innate
adaptive
immunity.
Gut
microbes
regulate
physiology
their
production
metabolites
byproducts.
Microbial
be
beneficial
or
detrimental
to
pathogenesis
progression
inflammatory
diseases.
A
better
understanding
GMB‐derived
lead
development
therapeutic
strategies
for
AD.
In
this
review,
we
summarize
function
bioactive
byproducts
roles
models.
We
also
call
more
focus
on
area
gut–brain
axis
field
order
create
therapies
Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Фев. 16, 2024
Abstract
The
human
gastrointestinal
tract
is
populated
with
a
diverse
microbial
community.
vast
genetic
and
metabolic
potential
of
the
gut
microbiome
underpins
its
ubiquity
in
nearly
every
aspect
biology,
including
health
maintenance,
development,
aging,
disease.
advent
new
sequencing
technologies
culture-independent
methods
has
allowed
researchers
to
move
beyond
correlative
studies
toward
mechanistic
explorations
shed
light
on
microbiome–host
interactions.
Evidence
unveiled
bidirectional
communication
between
central
nervous
system,
referred
as
“microbiota–gut–brain
axis”.
microbiota–gut–brain
axis
represents
an
important
regulator
glial
functions,
making
it
actionable
target
ameliorate
development
progression
neurodegenerative
diseases.
In
this
review,
we
discuss
mechanisms
As
provides
essential
cues
microglia,
astrocytes,
oligodendrocytes,
examine
communications
microbiota
these
cells
during
healthy
states
Subsequently,
diseases
using
metabolite-centric
approach,
while
also
examining
role
microbiota-related
neurotransmitters
hormones.
Next,
targeting
intestinal
barrier,
blood–brain
meninges,
peripheral
immune
system
counteract
dysfunction
neurodegeneration.
Finally,
conclude
by
assessing
pre-clinical
clinical
evidence
probiotics,
prebiotics,
fecal
transplantation
A
thorough
comprehension
will
foster
effective
therapeutic
interventions
for
management
Molecular Neurodegeneration,
Год журнала:
2024,
Номер
19(1)
Опубликована: Апрель 16, 2024
Abstract
Trillions
of
intestinal
bacteria
in
the
human
body
undergo
dynamic
transformations
response
to
physiological
and
pathological
changes.
Alterations
their
composition
metabolites
collectively
contribute
progression
Alzheimer’s
disease.
The
role
gut
microbiota
disease
is
diverse
complex,
evidence
suggests
lipid
metabolism
may
be
one
potential
pathways.
However,
mechanisms
that
mediate
pathology
remain
unclear,
necessitating
further
investigation
for
clarification.
This
review
highlights
current
understanding
how
disrupts
discusses
implications
these
discoveries
guiding
strategies
prevention
or
treatment
based
on
existing
data.
Neural Regeneration Research,
Год журнала:
2024,
Номер
20(4), С. 990 - 1008
Опубликована: Апрель 16, 2024
With
the
rapidly
aging
human
population,
age-related
cognitive
decline
and
dementia
are
becoming
increasingly
prevalent
worldwide.
Aging
is
considered
main
risk
factor
for
acts
through
alterations
in
composition
of
gut
microbiota,
microbial
metabolites,
functions
astrocytes.
The
microbiota–gut–brain
axis
has
been
focus
multiple
studies
closely
associated
with
function.
This
article
provides
a
comprehensive
review
specific
changes
that
occur
microbiota
metabolites
older
individuals
discusses
how
astrocytes
reactive
astrocytosis
related
to
neurodegenerative
diseases.
also
summarizes
components
affect
astrocyte
function,
mainly
vagus
nerve,
immune
responses,
circadian
rhythms,
metabolites.
Finally,
this
mechanism
by
which
microbiota–astrocyte
plays
role
Alzheimer’s
Parkinson’s
Our
findings
have
revealed
critical
decline,
aiding
deeper
understanding
potential
microbiome-based
adjuvant
therapy
strategies
condition.
Journal of Neuroinflammation,
Год журнала:
2024,
Номер
21(1)
Опубликована: Июль 30, 2024
Under
subarachnoid
hemorrhage
(SAH)
conditions,
astrocytes
undergo
a
marked
intensification
of
glycolytic
activity,
resulting
in
the
generation
substantial
amounts
lactate
to
maintain
energy
demand
for
neurons
and
other
brain
cells.
Lactate
has
garnered
increasing
attention
recent
years
because
its
emerging
role
critical
biological
processes
such
as
inflammation
regulation
neuroprotection,
particularly
through
histone
lactylation.
Bromodomain-containing
protein
4
(BRD4)
plays
crucial
maintaining
neural
development
promoting
memory
formation
central
nervous
system.
Nonetheless,
function
regulatory
mechanism
BRD4
lactylation
following
SAH
remain
elusive.
Our
findings
indicate
that
BRD4,
epigenetic
regulator,
definitive
Both
vitro
vivo,
these
results
demonstrated
targeted
silencing
can
significantly
reduce
H4K8la
lactylation,
thereby
aggravating
A1
polarization
ultimately
affecting
recovery
prognosis
mice
after
SAH.
In
summary,
pivotal
modulating
astrocyte
via
Targeting
this
might
offer
an
efficient
therapeutic
strategy
Cell Death and Disease,
Год журнала:
2024,
Номер
15(3)
Опубликована: Март 13, 2024
Abstract
In
recent
years,
several
studies
described
the
close
relationship
between
composition
of
gut
microbiota
and
brain
functions,
highlighting
importance
gut-derived
metabolites
in
mediating
neuronal
glial
cells
cross-talk
physiological
pathological
condition.
Gut
dysbiosis
may
affects
cerebral
tumors
growth
progression,
but
specific
involved
this
modulation
have
not
been
identified
yet.
Using
a
syngeneic
mouse
model
glioma,
we
investigated
role
induced
by
administration
non-absorbable
antibiotics
on
metabolome
tumor
microenvironment.
We
report
that
treatment
induced:
(1)
alteration
profiles;
(2)
modeling
microenvironment
toward
pro-angiogenic
phenotype
which
microglia
glioma
are
actively
involved;
(3)
increased
stemness;
(4)
trans-differentiation
into
endothelial
precursor
cells,
thus
increasing
vasculogenesis.
propose
glycine
as
metabolite
that,
ABX-induced
dysbiosis,
shapes
contributes
to
progression.
Frontiers in Aging Neuroscience,
Год журнала:
2024,
Номер
16
Опубликована: Авг. 9, 2024
The
most
prevalent
cause
of
dementia
is
Alzheimer's
disease.
Cognitive
decline
and
accelerating
memory
loss
characterize
it.
disease
advances
sequentially,
starting
with
preclinical
stages,
followed
by
mild
cognitive
and/or
behavioral
impairment,
ultimately
leading
to
dementia.
In
recent
years,
healthcare
providers
have
been
advised
make
an
earlier
diagnosis
Alzheimer's,
prior
individuals
developing
Regrettably,
the
identification
early-stage
in
clinical
settings
can
be
arduous
due
tendency
patients
disregard
symptoms
as
typical
signs
aging.
Therefore,
accurate
prompt
essential
order
facilitate
development
disease-modifying
secondary
preventive
therapies
onset
symptoms.
There
has
a
notable
shift
goal
process,
transitioning
from
merely
confirming
presence
symptomatic
AD
recognizing
illness
its
early,
asymptomatic
phases.
Understanding
evolution
putting
effective
diagnostic
therapeutic
management
into
practice
requires
understanding
this
concept.
outcomes
study
will
enhance
in-depth
knowledge
current
status
disease's
treatment,
justifying
necessity
for
quest
potential
novel
biomarkers
that
contribute
determining
stage
disease,
particularly
earliest
stages.
Interestingly,
latest
trial
on
pharmacological
agents,
nonpharmacological
treatments
such
behavior
modification,
exercise,
training
well
alternative
approach
phytochemicals
neuroprotective
agents
covered
detailed.
Gut
bacteria
regulate
brain
pathology
of
Alzheimer's
disease
(AD)
patients
and
animal
models;
however,
the
underlying
mechanism
remains
unclear.
In
this
study,
3-month-old
APP-transgenic
female
mice
with
without
knock-out
Il-17a
gene
were
treated
antibiotics-supplemented
or
normal
drinking
water
for
2
months.
The
antibiotic
treatment
eradicated
almost
all
intestinal
bacteria,
which
led
to
a
reduction
in
Il-17a-expressing
CD4-positive
T
lymphocytes
spleen
gut,
decrease
bacterial
DNA
tissue.
Depletion
gut
inhibited
inflammatory
activation
both
tissue
microglia,
lowered
cerebral
Aβ
levels,
promoted
transcription
Arc
mice,
effects
abolished
by
deficiency
Il-17a.
As
possible
mechanisms
regulating
pathology,
depletion
β-secretase
activity
increased
expression
Abcb1
Lrp1
at
blood-brain
barrier,
also
reversed
absence
Interestingly,
crossbreeding
experiment
between
knockout
further
showed
that
had
already
barrier.
Thus,
attenuates
amyloid
via
Il-17a-involved
signaling
pathways.
Our
study
contributes
better
understanding
gut-brain
axis
AD
pathophysiology
highlights
therapeutic
potential
inhibition
specific
stimulate
development
cells.
Biomedicine & Pharmacotherapy,
Год журнала:
2023,
Номер
168, С. 115825 - 115825
Опубликована: Ноя. 2, 2023
Alzheimer's
disease
(AD)
is
a
progressive
neurodegenerative
for
which
there
lack
of
effective
therapeutic
drugs.
There
great
potential
natural
products
to
be
used
in
the
development
anti-AD
P-coumaric
acid
(PCA),
small
molecule
phenolic
widely
distributed
plant
kingdom,
has
pharmacological
effects
such
as
neuroprotection,
but
its
mechanism
not
been
fully
elucidated.
In
current
study,
we
investigated
PCA
intervention
Aβ25-35-induced
AD
model
using
gut
microbiomics
and
serum
metabolomics
combined
with
vitro
vivo
experiments.
was
found
ameliorate
cognitive
dysfunction
neuronal
cell
damage
Aβ25-35-injected
mice
measured
by
behavioral,
pathological
biochemical
indicators.
16S
rDNA
sequencing
showed
that
reduced
abundance
pro-inflammatory-associated
microbiota
(morganella,
holdemanella,
fusicatenibacter
serratia)
gut,
were
closely
associated
metabolites
glucose
metabolism,
arachidonic
tyrosine
metabolism
phospholipid
pathways
serum.
Next,
investigations
revealed
regulated
disruption
through
activation
PI3K/AKT/Glut1
signaling.
Additionally,
ameliorated
neuroinflammation
inhibiting
nuclear
translocation
NF-κB
modulating
upstream
MAPK
conclusion,
deficits
regulating
neuroinflammation,
related
only
restoring
homeostasis
metabolites,
also
MAPK/NF-κB
