Bile
acids
(BAs)
metabolism
has
a
significant
impact
on
the
pathogenesis
of
Alzheimer’s
disease
(AD).
We
found
that
deoxycholic
acid
(DCA)
increased
in
brains
AD
mice
at
an
early
stage.
The
enhanced
production
DCA
induces
up-regulation
bile
receptor
Takeda
G
protein-coupled
(TGR5),
which
is
also
specifically
neurons
mouse
accumulation
exogenous
impairs
cognitive
function
wild-type
mice,
but
not
TGR5
knockout
mice.
This
suggests
primary
mediating
these
effects
DCA.
Furthermore,
excitatory
neuron-specific
ameliorates
Aβ
pathology
and
cognition
impairments
underlying
mechanism
linking
relies
downstream
effectors
APP
production,
succinctly
concluded
as
“p-STAT3–APH1–γ-secretase”
signaling
pathway.
Our
studies
identified
critical
role
pathological
development
AD.
Alzheimer s & Dementia Translational Research & Clinical Interventions,
Год журнала:
2024,
Номер
10(2)
Опубликована: Апрель 1, 2024
Abstract
INTRODUCTION
Alzheimer's
disease
(AD)
is
the
predominant
dementia
globally,
with
heterogeneous
presentation
and
penetrance
of
clinical
symptoms,
variable
presence
mixed
pathologies,
potential
subtypes,
numerous
associated
endophenotypes.
Beyond
difficulty
designing
treatments
that
address
core
pathological
characteristics
disease,
therapeutic
development
challenged
by
uncertainty
which
endophenotypic
areas
specific
targets
implicated
those
endophenotypes
to
prioritize
for
further
translational
research.
However,
publicly
funded
consortia
driving
large‐scale
open
science
efforts
have
produced
multiple
omic
analyses
both
risk
relevance
biological
process
involvement
genes
across
genome.
METHODS
Here
we
report
an
informatic
pipeline
draws
from
genetic
association
studies,
predicted
variant
impact,
linkage
phenotypes
create
a
score.
This
paired
multi‐omic
score
utilizing
extensive
sets
transcriptomic
proteomic
studies
identify
system‐level
changes
in
expression
AD.
These
two
elements
combined
constitute
our
target
ranks
AD
genome‐wide.
The
ranked
are
organized
into
space
through
19
domains
described
genetics
genomics
accompanying
literature.
constructed
exhaustive
Gene
Ontology
(GO)
term
compilations,
allowing
automated
assignment
objectively
defined
disease‐associated
biology.
rank‐and‐organize
approach,
performed
genome‐wide,
allows
characterization
aggregations
domains.
RESULTS
top
AD‐risk‐associated
Synapse,
Immune
Response,
Lipid
Metabolism,
Mitochondrial
Structural
Stabilization,
Proteostasis,
slightly
lower
levels
enrichment
present
within
other
13
DISCUSSION
provides
objective
methodology
localize
drill
down
most
significantly
GO
terms
annotated
targets.
Current Issues in Molecular Biology,
Год журнала:
2024,
Номер
46(5), С. 4379 - 4402
Опубликована: Май 6, 2024
Alzheimer’s
disease
(AD)
is
a
progressive
neurodegenerative
and
the
most
common
form
of
dementia
globally.
Although
direct
cause
AD
remains
under
debate,
neuroinflammation
oxidative
stress
are
critical
components
in
its
pathogenesis
progression.
As
result,
compounds
like
cannabidiol
(CBD)
being
increasingly
investigated
for
their
ability
to
provide
antioxidant
anti-inflammatory
neuroprotection.
CBD
primary
non-psychotropic
phytocannabinoid
derived
from
Cannabis
sativa.
It
has
been
found
beneficial
outcomes
variety
medical
conditions
gaining
increasing
attention
potential
therapeutic
application
AD.
not
psychoactive
lipophilic
nature
allows
rapid
distribution
throughout
body,
including
across
blood–brain
barrier
(BBB).
also
possesses
anti-inflammatory,
antioxidant,
neuroprotective
properties,
making
it
viable
candidate
treatment.
This
review
outlines
CBD’s
mechanism
action,
role
AD,
effectiveness
limitations
preclinical
models
Abstract
The
ability
to
reprogram
patient-derived-somatic
cells
IPSCs
(Induced
Pluripotent
Stem
Cells)
has
led
a
better
understanding
of
aging
and
age-related
diseases
like
Parkinson’s,
Alzheimer’s.
established
patient-derived
disease
models
mimic
pathology
can
be
used
design
drugs
for
diseases.
However,
the
age
genetic
mutations
donor
cells,
employed
reprogramming,
differentiation
protocol
might
often
pose
challenges
in
establishing
an
appropriate
model.
In
this
review,
we
will
focus
on
various
strategies
successful
reprogramming
diseases,
emphasizing
accuracy
recapitulation
ways
overcome
limitations
its
potential
application
cell
replacement
therapy
drug
development.
CNS Neuroscience & Therapeutics,
Год журнала:
2025,
Номер
31(1)
Опубликована: Янв. 1, 2025
ABSTRACT
Aims
To
analyze
the
effect
of
APOE
ε
4
on
fluid
biomarkers
and
correlations
between
blood
molecules
CSF
in
AD
patients.
Methods
This
study
enrolled
575
patients,
131
patients
with
non‐AD
dementia,
112
cognitively
normal
(CN)
participants,
were
divided
into
carriers
non‐carriers.
Cerebrospinal
(CSF)
blood‐derived
biomolecules
compared
CN
groups,
dementia
as
well
within
subgroups
Utilizing
Spearman's
correlation
analysis
quantile
regression
analysis,
relationships
analyzed
Results
The
levels
exhibited
significant
differences
including
Aβ42,
t‐tau,
p‐tau
181,
high‐density
lipoprotein,
low‐density
lipoprotein
(LDL),
uric
acid.
In
had
increased
plasma
LDL.
analyses,
negative
TG
181
levels,
positive
relationship
serum
IgA
observed
significantly
4+
but
not
4−
group.
Conclusion
is
associated
accelerated
progression
pathology.
correlated
are
related
to
neuroinflammation
lipid
metabolism,
which
may
indicate
role
pathophysiology
offer
insights
for
diagnostic
therapeutic
strategies
AD.
Trial
Registration
ClinicalTrials.gov
identifier:
NCT03653156
Alzheimer s Research & Therapy,
Год журнала:
2025,
Номер
17(1)
Опубликована: Янв. 7, 2025
Abstract
We
have
previously
demonstrated
that
the
intracellular,
non-GPI
anchored
CD59
isoforms
IRIS-1
and
IRIS-2
(Isoforms
Rescuing
Insulin
Secretion
1
2)
are
necessary
for
insulin
secretion
from
pancreatic
β-cells.
While
investigating
their
expression
across
human
tissues,
we
identified
mRNA
in
brain,
though
protein
function
remained
unclear.
This
study
shows
presence
of
both
2
proteins
specifically
neurons
astrocytes.
In
neuroblastoma
cell
line
(SH-SY5Y),
increases
upon
differentiation
into
mature
neurons.
Silencing
SH-SY5Y
cells
reduces
SNARE
complex
formation,
essential
synaptic
vesicle
exocytosis,
leading
to
a
reduction
noradrenaline
secretion.
Notably,
observed
diminished
neuronal
patients
with
Alzheimer’s
disease
(AD)
non-demented
individuals
type
diabetes
(T2D).
cells,
knockdown
all
including
not
only
elevates
phosphorylated
tau
but
also
cyclin-dependent
kinase
5
(CDK5)
expression,
known
promoter
hyperphosphorylation
accumulation
tau,
key
pathological
feature
AD.
Additionally,
found
prolonged
exposure
high
glucose
or
cytokines
markedly
suggesting
link
between
AD
pathology
metabolic
stress
through
modulation
these
isoforms.
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(2), С. 484 - 484
Опубликована: Янв. 8, 2025
Alzheimer's
disease
(AD)
remains
a
leading
cause
of
cognitive
decline
and
mortality
worldwide,
characterized
by
neurodegeneration,
synaptic
deficiencies,
neuroinflammation.
Despite
advancements
in
early
detection,
diagnosis,
treatment,
AD
presents
substantial
challenges
due
to
its
complex
pathology,
heterogeneity,
the
limited
efficacy
current
therapies.
Consequently,
there
is
pressing
need
for
novel
therapeutic
agents
target
multifaceted
aspects
enhance
treatments,
minimize
adverse
effects.
AdipoRon,
an
adiponectin
receptor
agonist,
has
garnered
interest
potential
neuroprotective
effects,
including
reducing
neuroinflammation,
improving
mitochondrial
function,
mitigating
tau
hyperphosphorylation.
This
review
aimed
evaluate
effects
AdipoRon-based
replacement
therapy
against
AD,
using
comprehensive
approach
grounded
PICO
framework-Population,
Intervention,
Comparison,
Outcomes.
A
total
six
studies
were
reviewed,
vitro
vivo
investigations
examining
AdipoRon's
impact
on
various
models.
These
involved
different
cell
lines
transgenic
mouse
models,
assessing
outcomes
such
as
phosphorylation,
relevant
molecular
pathways.
By
synthesizing
data
from
these
studies,
our
thoroughly
explains
mechanisms
action,
agent
AD.
analysis
aims
highlight
state
knowledge,
identify
gaps
research,
suggest
directions
future
clinical
applications.
Receptors,
Год журнала:
2025,
Номер
4(1), С. 2 - 2
Опубликована: Янв. 26, 2025
Glucagon-like
peptide-1
receptor
agonists
(GLP-1RAs),
including
dulaglutide,
liraglutide,
semaglutide,
and
exenatide,
are
effective
treatments
for
type
2
diabetes
mellitus
(T2DM)
obesity.
These
agents
mimic
the
action
of
endogenous
incretin
glucagon-like
(GLP-1)
by
enhancing
insulin
secretion,
inhibiting
glucagon
release,
promoting
weight
loss
through
appetite
suppression.
GLP-1RAs
have
recently
been
suggested
to
neuroprotective
effects,
suggesting
their
potential
as
treatment
neurodegenerative
disorders,
such
Alzheimer’s
disease
(AD).
AD
T2DM
share
several
common
pathophysiological
mechanisms,
resistance,
chronic
inflammation,
oxidative
stress,
mitochondrial
dysfunction.
shared
mechanisms
suggest
that
therapeutic
targeting
metabolic
dysfunction
may
also
be
beneficial
conditions.
Preclinical
studies
on
in
models,
both
vitro
vivo,
demonstrated
promising
reductions
amyloid-beta
accumulation,
decreased
tau
hyperphosphorylation,
improved
synaptic
plasticity,
enhanced
neuronal
survival.
Despite
encouraging
results
from
preclinical
challenges
need
addressed
before
can
widely
used
treatment.
Ongoing
clinical
trials
investigating
cognitive
benefits
patients,
aiming
establish
role
a
option
AD.
This
review
aimed
examine
current
literature
GLP-1
Antioxidants,
Год журнала:
2022,
Номер
11(8), С. 1511 - 1511
Опубликована: Авг. 2, 2022
Neurodegenerative
diseases
are
characterized
by
gradually
progressive,
selective
loss
of
anatomically
or
physiologically
related
neuronal
systems
that
produce
brain
damage
from
which
there
is
no
recovery.
Despite
the
differences
in
clinical
manifestations
and
vulnerability,
pathological
processes
appear
to
be
similar,
suggesting
common
neurodegenerative
pathways.
It
well
known
oxidative
stress
production
reactive
oxygen
radicals
plays
a
key
role
cell
damage.
has
been
proposed
this
stress,
among
other
mechanisms,
could
contribute
degeneration
might
one
factors
triggering
development
these
pathologies.
Another
feature
most
neuron
hyperexcitability,
an
aberrant
electrical
activity.
This
review,
focusing
mainly
on
primary
motor
cortex
pyramidal
neurons,
critically
evaluates
idea
inflammation
may
involved
neurodegeneration
via
their
capacity
increase
membrane
excitability.
Cells,
Год журнала:
2022,
Номер
11(21), С. 3395 - 3395
Опубликована: Окт. 27, 2022
Neurodegenerative
diseases
(NDDs)
are
irreversible,
progressive
with
no
effective
treatment.
The
hallmark
of
NDDs
is
the
aggregation
misfolded,
modified
proteins,
which
impair
neuronal
vulnerability
and
cause
brain
damage.
loss
synaptic
connection
neurons
result
in
cognitive
defects.
Several
dysregulated
proteins
overlapping
molecular
mechanisms
contribute
to
pathophysiology
NDDs.
Post-translational
modifications
(PTMs)
essential
regulators
protein
function,
trafficking,
maintaining
hemostasis.
conjugation
a
small
ubiquitin-like
modifier
(SUMO)
reversible,
dynamic
PTM
required
for
function.
onset
progression
neurodegenerative
associated
aberrant
SUMOylation.
In
this
review,
we
have
summarized
role
SUMOylation
regulating
critical
involved
several
