Neural Regeneration Research,
Год журнала:
2023,
Номер
20(3), С. 695 - 714
Опубликована: Дек. 21, 2023
Alzheimer's
disease,
the
primary
cause
of
dementia,
is
characterized
by
neuropathologies,
such
as
amyloid
plaques,
synaptic
and
neuronal
degeneration,
neurofibrillary
tangles.
Although
plaques
are
characteristic
disease
in
central
nervous
system
peripheral
organs,
targeting
amyloid-beta
clearance
has
shown
limited
clinical
efficacy
treatment.
Metabolic
abnormalities
commonly
observed
patients
with
disease.
The
liver
organ
involved
metabolism,
playing
a
crucial
role
pathophysiology
Notably,
impaired
cholesterol
metabolism
may
exacerbate
development
In
this
review,
we
explore
underlying
causes
elucidate
metabolism.
Furthermore,
propose
that
restoring
normal
could
represent
promising
therapeutic
strategy
for
addressing
Cell Metabolism,
Год журнала:
2024,
Номер
36(5), С. 1000 - 1012.e6
Опубликована: Апрель 5, 2024
The
gut-brain
axis
is
implicated
in
depression
development,
yet
its
underlying
mechanism
remains
unclear.
We
observed
depleted
gut
bacterial
species,
including
Bifidobacterium
longum
and
Roseburia
intestinalis,
the
neurotransmitter
homovanillic
acid
(HVA)
individuals
with
mouse
models.
Although
R.
intestinalis
does
not
directly
produce
HVA,
it
enhances
B.
abundance,
leading
to
HVA
generation.
This
highlights
a
synergistic
interaction
among
microbiota
regulating
intestinal
production.
Administering
longum,
or
models
chronic
unpredictable
mild
stress
(CUMS)
corticosterone
(CORT)-induced
significantly
improved
depressive
symptoms.
Mechanistically,
inhibited
synaptic
autophagic
death
by
preventing
excessive
degradation
of
microtubule-associated
protein
1
light
chain
3
(LC3)
SQSTM1/p62
proteins,
protecting
hippocampal
neurons'
presynaptic
membrane.
These
findings
underscore
role
microbial
metabolism
modulating
integrity
provide
insights
into
potential
novel
treatment
strategies
for
depression.
Psychiatry Research,
Год журнала:
2024,
Номер
334, С. 115804 - 115804
Опубликована: Фев. 18, 2024
•
MDD
has
substantial
changes
in
the
structure
and
function
of
gut
microbiota.
exhibited
decreased
amino
acids
bile
increased
lipids
blood.
The
blood
immune
cell
subtypes
tend
to
promote
inflammation.
could
be
divided
into
two
subtypes,
one
is
correlated
with
relapse.
We
revealed
integrative
discriminative
signatures
for
distinguishing
from
HC.
Major
depressive
disorder
(MDD)
involves
systemic
peripheral
microbiota,
but
current
understanding
incomplete.
Herein,
we
conducted
a
multi-omics
analysis
fecal
samples
obtained
an
observational
cohort
including
patients
(n
=
99)
healthy
control
(HC,
n
50).
16S
rRNA
sequencing
microbiota
showed
structural
alterations
MDD,
as
characterized
by
Enterococcus
.
Metagenomics
functional
upregulation
superpathway
glyoxylate
cycle
fatty
acid
degradation
downregulation
various
metabolic
pathways
MDD.
Plasma
metabolomics
acids,
together
sphingolipids
cholesterol
esters
Notably,
metabolites
involved
arginine
proline
metabolism
were
while
sphingolipid
pathway
increased.
Mass
cytometry
rises
proinflammatory
subsets
declines
anti-inflammatory
Furthermore,
our
findings
disease
severity-related
factors
Interestingly,
classified
that
highly
Moreover,
established
differentiate
These
contribute
comprehensive
pathogenesis
provide
valuable
resources
discovery
biomarkers.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Май 7, 2024
The
metabolic
implications
in
Alzheimer's
disease
(AD)
remain
poorly
understood.
Here,
we
conducted
a
metabolomics
study
on
moderately
aging
Chinese
Han
cohort
(n
=
1397;
mean
age
66
years).
Conjugated
bile
acids,
branch-chain
amino
acids
(BCAAs),
and
glutamate-related
features
exhibited
strong
correlations
with
cognitive
impairment,
clinical
stage,
brain
amyloid-β
deposition
421).
These
demonstrated
synergistic
performances
across
stages
subpopulations
enhanced
the
differentiation
of
AD
beyond
demographics
Apolipoprotein
E
ε4
allele
(APOE-ε4).
We
validated
their
eight
data
sets
(total
n
7685)
obtained
from
Disease
Neuroimaging
Initiative
(ADNI)
Religious
Orders
Study
Memory
Aging
Project
(ROSMAP).
Importantly,
identified
are
linked
to
blood
ammonia
homeostasis.
further
confirmed
elevated
level
through
development
1060).
Our
findings
highlight
as
emphasize
metabolite-mediated
disturbance
its
potential
signature
therapeutic
target
for
AD.
Frontiers in Neuroscience,
Год журнала:
2024,
Номер
18
Опубликована: Фев. 19, 2024
Alzheimer’s
disease
(AD)
is
a
prevalent
neurodegenerative
that
has
become
one
of
the
main
factors
affecting
human
health.
It
serious
impacts
on
individuals,
families,
and
society.
With
development
population
aging,
incidence
AD
will
further
increase
worldwide.
Emerging
evidence
suggests
many
physiological
metabolic
processes,
such
as
lipid
metabolism,
are
implicated
in
pathogenesis
AD.
Bile
acids,
undertakers
play
an
important
role
occurrence
disease.
Tauroursodeoxycholic
acid,
endogenous
bile
been
proven
to
possess
therapeutic
effects
different
diseases,
including
This
review
tries
find
relationship
between
acid
metabolism
AD,
well
explore
potential
taurocursodeoxycholic
for
this
The
mechanisms
may
include
reducing
deposition
Amyloid-β
protein,
regulating
apoptotic
pathways,
preventing
tau
hyperphosphorylation
aggregation,
protecting
neuronal
synapses,
exhibiting
anti-inflammatory
properties,
improving
disorders.
objective
study
shed
light
use
tauroursodeoxycholic
preparations
prevention
treatment
with
aim
identifying
effective
targets
clarifying
various
involved
Frontiers in Neuroscience,
Год журнала:
2023,
Номер
17
Опубликована: Фев. 2, 2023
The
liver
partakes
as
a
sensor
and
effector
of
peripheral
metabolic
changes
regulator
systemic
blood
nutrient
circulation.
As
such,
abnormalities
arising
from
dysfunction
can
influence
the
brain
in
multiple
ways,
owing
to
direct
indirect
bilateral
communication
between
brain.
Interestingly,
altered
bile
acid
composition
resulting
perturbed
cholesterol
metabolism
influences
inflammatory
responses,
blood-brain
barrier
permeability,
neuron
synaptic
functions.
Furthermore,
acids
produced
by
specific
bacterial
species
may
provide
causal
link
dysregulated
gut
flora
neurodegenerative
disease
pathology
through
gut-brain
axis.
This
review
will
cover
role
acids—an
often-overlooked
category
active
metabolites—in
development
neurological
disorders
associated
with
neurodegeneration.
Further
studies
into
signaling
insights
novel
treatments
against
disorders.
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(6), С. 2722 - 2722
Опубликована: Март 18, 2025
Growing
neurochemical
evidence
highlights
cerebral
lipid
dysregulation
as
a
key
factor
in
the
pathophysiology
of
major
depressive
disorder
(MDD).
This
review
systematically
explores
dual
roles
species
both
normal
behavioral
regulation
and
MDD
development.
By
critically
examining
recent
literature,
we
classify
these
into
two
functional
categories
based
on
their
neuroactivity:
(1)
neuroprotective
lipids
(sphingomyelin,
cholesterol,
cardiolipin,
sphingosine,
phosphatidic
acid,
phosphatidylserine),
which
exert
effects
by
modulating
membrane
fluidity
supporting
synaptic
vesicle
trafficking;
(2)
neurotoxic
(ceramides,
phosphatidylinositol,
phosphocholine,
phosphatidylethanolamine),
promote
apoptotic
signaling
cascades
disrupt
mitochondrial
bioenergetics.
An
unresolved
but
critical
question
pertains
to
maintenance
homeostatic
equilibrium
between
opposing
classes.
balance
is
essential,
given
significant
impact
protein
localization
function,
monoaminergic
neurotransmitter
metabolism,
energy
homeostasis,
redox
neural
circuits
involved
mood
regulation.
emerging
framework
positions
lipidomics
promising
avenue
for
identifying
novel
therapeutic
targets
developing
biomarker-based
diagnostic
approaches
treatment.
Journal of Alzheimer s Disease Reports,
Год журнала:
2023,
Номер
7(1), С. 173 - 211
Опубликована: Фев. 17, 2023
Recent
clinical
studies
have
revealed
that
the
serum
levels
of
toxic
hydrophobic
bile
acids
(deoxy
cholic
acid,
lithocholic
acid
[LCA],
and
glycoursodeoxycholic
acid)
are
significantly
higher
in
patients
with
Alzheimer’s
disease
(AD)
amnestic
mild
cognitive
impairment
(aMCI)
when
compared
to
control
subjects.
The
elevated
may
be
result
hepatic
peroxisomal
dysfunction.
Circulating
able
disrupt
blood-brain
barrier
promote
formation
amyloid-β
plaques
through
enhancing
oxidation
docosahexaenoic
acid.
Hydrophobic
find
their
ways
into
neurons
via
apical
sodium-dependent
transporter.
It
has
been
shown
impose
pathological
effects
by
activating
farnesoid
X
receptor
suppressing
synthesis
brain,
blocking
NMDA
receptors,
lowering
brain
oxysterol
levels,
interfering
17β-estradiol
actions
such
as
LCA
binding
E2
receptors
(molecular
modelling
data
exclusive
this
paper).
interfere
sonic
hedgehog
signaling
alteration
cell
membrane
rafts
reducing
24(S)-hydroxycholesterol.
This
article
will
1)
analyze
roles
circulating
2)
propose
therapeutic
approaches,
3)
conclude
consideration
given
reducing/monitoring
AD
or
aMCI,
prior/in
combination
other
treatments.
Frontiers in Microbiology,
Год журнала:
2023,
Номер
14
Опубликована: Апрель 14, 2023
The
gut
microbiome
is
critically
involved
in
maintaining
normal
physiological
function
the
host.
Recent
studies
have
revealed
that
alterations
contribute
to
development
and
progression
of
cerebrovascular
disease
via
microbiota-gut-brain
axis
(MGBA).
As
a
broad
communication
network
human
body,
MGBA
has
been
demonstrated
significant
interactions
with
various
factors,
such
as
brain
structure
function,
nervous
system
diseases,
etc.
It
also
believed
species
composition
microbiota
its
metabolites
are
intrinsically
linked
vascular
inflammation
immune
responses.
In
fact,
fecal
transplantation
(FMT)
research,
specific
downstream-related
proven
not
only
participate
processes
but
affect
occurrence
diseases
directly
or
indirectly
through
systemic
inflammatory
response.
Due
high
mortality
disability
rate
new
treatments
improve
intestinal
dysbacteriosis
gradually
attracted
widespread
attention
better
ameliorate
poor
prognosis
non-invasive
way.
This
review
summarizes
latest
advances
research
reveals
profound
impact
dysbiosis
on
diseases.
At
same
time,
we
elucidated
molecular
mechanisms
whereby
microbial
regulate
expression
interleukins
Moreover,
further
discuss
feasibility
novel
therapeutic
strategies
targeting
outcome
patients
Finally,
provide
insights
for
standardized
diagnosis
treatment
General Psychiatry,
Год журнала:
2024,
Номер
37(1), С. e101310 - e101310
Опубликована: Фев. 1, 2024
Alzheimer’s
disease
(AD)
is
a
common
cause
of
dementia,
characterised
by
cerebral
amyloid-β
deposition,
pathological
tau
and
neurodegeneration.
The
prodromal
stage
AD
(pAD)
refers
to
patients
with
mild
cognitive
impairment
(MCI)
evidence
AD’s
pathology.
At
this
stage,
disease-modifying
interventions
should
be
used
prevent
the
progression
dementia.
Given
inherent
heterogeneity
MCI,
more
specific
biomarkers
are
needed
elucidate
underlying
Although
uses
cerebrospinal
fluid
positron
emission
tomography
widely
accepted
methods
for
detecting
pathology,
their
clinical
applications
limited
high
costs
invasiveness,
particularly
in
low-income
areas
China.
Therefore,
improve
early
detection
Alzheimer's
pathology
through
cost-effective
screening
methods,
panel
45
neurologists,
psychiatrists
gerontologists
was
invited
establish
formal
consensus
on
pAD
supportive
grades
recommendations
based
systematic
literature
review
focus
group
discussion.
National
meetings
were
held
allow
participants
review,
vote
provide
expert
opinions
reach
consensus.
A
majority
(two-thirds)
decision
questions
which
could
not
reached.
Recommended
presented
publication,
including
neuropsychological
assessment,
peripheral
brain
imaging.
In
addition,
general
workflow
China
established,
will
help
clinicians
identify
individuals
at
risk
determine
therapeutic
targets.
