Journal of Agricultural and Food Chemistry,
Journal Year:
2024,
Volume and Issue:
73(9), P. 5635 - 5648
Published: Nov. 13, 2024
As
a
traditional
drug-food
homologous
plant,
Dendrobium
officinale
is
widely
recognized
for
its
nutritional
and
medicinal
value.
Specifically,
D.
polysaccharide
(DOP)
has
garnered
attention
as
potential
prebiotic
protective
effects
on
gut
microbiota
the
nervous
system.
However,
underlying
mechanism
by
which
DOP
improves
cognitive
dysfunction
in
Alzheimer's
disease
(AD)
remains
unclear.
This
study
intends
to
elucidate
beneficial
of
AD
mice
from
perspectives
metabolomics
intestinal
microbiome.
The
results
showed
that
significantly
ameliorated
dysfunction,
attenuated
hippocampal
neuronal
damage
Aβ
plaque
deposition,
restored
barrier
integrity
mice.
antibiotic-cocktail-induced
germ-free
mouse
model
confirmed
neuroprotective
effect
was
dependent
microbiota.
Further
investigations
demonstrated
influenced
composition
diversity.
Additionally,
reshaped
metabolic
profile
disorders
increased
short-chain
fatty
acids
(SCFAs)
content.
Correlation
analysis
further
highlighted
specific
associated
with
metabolism
In
conclusion,
this
sheds
light
positive
impact
reshaping
enhancing
function,
offering
important
possible
advancement
utilization
DOP.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 13, 2025
ABSTRACT
INTRODUCTION
Alzheimer’s
disease
(AD)
lacks
a
less
invasive
and
early
detectable
biomarker.
Here,
we
investigated
the
biomarker
potential
of
miR-501-3p
miR-502-3p
using
different
AD
sources.
METHODS
MiR-501-3p
expressions
were
evaluated
in
CSF
exosomes,
serum
familial
sporadic
fibroblasts
B-lymphocytes
by
qRT-PCR
analysis.
Further,
analyzed
APP,
Tau
cells
media
exosomes.
RESULTS
significantly
upregulated
exosomes
relative
to
controls.
MiRNA
levels
high
accordance
with
amyloid
plaque
NFT
density
multiple
brain
regions.
Similarly,
both
miRNAs
elevated
MCI
compared
MiR-502-3p
expression
was
fAD
sAD
B-lymphocytes.
Finally,
intracellularly
secreted
extracellularly
response
APP
pathology.
DISCUSSION
These
results
suggest
that
could
be
promising
biomarkers
for
AD.
Journal of Alzheimer s Disease,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 15, 2025
Background
Extracellular
signal-regulated
kinase
1
(ERK1)
belongs
to
mitogen-activated
protein
kinases,
which
are
essential
for
memory
formation,
cognitive
function,
and
synaptic
plasticity.
During
Alzheimer's
disease
(AD),
ERK1
phosphorylates
tau
at
15
phosphorylation
sites,
leading
the
formation
of
neurofibrillary
tangles.
The
overactivation
in
microglia
promotes
release
pro-inflammatory
cytokines,
results
neuroinflammation.
Additionally,
elevated
oxidative
stress
during
AD
stimulates
pathway,
neuronal
loss.
Objective
Because
signaling
plays
a
significant
role
phosphorylation,
targeting
may
be
therapeutically
beneficial
by
either
preventing
excessive
activation
pathway
or
altering
its
enhance
neuroprotective
effects
AD.
Methods
This
study
employed
structure-based
virtual
screening
phytoconstituents
from
IMPPAT
library.
Subsequently,
in-depth
docking
molecular
dynamics
(MD)
simulation
studies
were
implemented
identify
potential
inhibitors
with
desirable
pharmacological
properties.
Results
Silandrin
Hydroxytuberosone
found
higher
affinity
specificity
than
control
molecule
Tizaterkib.
These
compounds
specifically
bind
substrate
binding
pocket
interact
crucial
residues.
Finally,
elucidated
evaluated
using
an
all-atom
MD
analyze
structural
dynamics,
compactness,
hydrogen
bond
principal
component
analysis,
free
energy
landscape.
Conclusions
suggested
that
can
further
exploited
as
lead
molecules
therapeutic
development
against
ERK1-mediated
Frontiers in Aging Neuroscience,
Journal Year:
2025,
Volume and Issue:
17
Published: Feb. 13, 2025
Alzheimer’s
disease
(AD)
is
a
neurodegenerative
disorder
that
significantly
impairs
memory,
cognitive
function,
and
the
ability
to
perform
daily
tasks.
The
pathological
features
of
AD
include
β-amyloid
plaques,
neurofibrillary
tangles,
neuronal
loss.
Current
treatments
target
changes
but
often
fail
noticeably
slow
progression
can
cause
severe
complications,
limiting
their
effectiveness.
In
addition
therapies
targeting
core
pathology
AD,
more
comprehensive
approach
may
be
needed
for
its
treatment.
recent
years,
non-pharmacological
such
as
physical
therapy,
exercise
cell
nanoparticles
have
shown
great
potential
in
mitigating
alleviating
clinical
symptoms.
This
article
reviews
advances
treatment
approaches
highlighting
contributions
management
facilitating
exploration
novel
therapeutic
strategies.
ACS Chemical Neuroscience,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 21, 2025
The
fibrillation
of
α-synuclein
(α-syn)
is
a
major
factor
contributing
to
neuronal
damage
and
critical
in
developing
synucleopathies-related
disorders.
Considering
this,
the
discovery
new
compounds
that
can
inhibit
or
modulate
α-syn
aggregation
significant
area
research.
While
polyol
osmolytes
have
been
shown
reduce
fibrillation,
impact
brain
metabolites
such
as
myo-inositol
(MI)
on
has
not
yet
explored.
This
study
first
examine
effects
MI
aggregation,
utilizing
spectroscopic,
microscopic,
cell
cytotoxicity
assay.
Various
assays
revealed
inhibits
dose-dependent
manner.
Fluorescence
microscopy
observations
suggest
by
forming
amorphous
aggregates.
MTT
assay
aggregates
presence
different
concentrations
were
toxic
compared
fibrils.
Thus,
mechanistic
insight
inhibition
was
explored
employing
interaction
studies
using
calorimetric,
silico
approaches.
Surface
plasmon
resonance
isothermal
titration
calorimetry
MI-α-syn
interacted
with
binding
affinity,
reaction
spontaneous.
Molecular
docking
results
depict
aggregation-prone
residues
(36-42)
at
N-terminal
α-syn,
thereby
stabilizing
preventing
fibril
formation.
dynamics
simulation
demonstrate
stability
complex
formation
α-syn.
highlighted
from
amyloid
fibril,
which
could
be
further
for
therapeutic
management
Stem Cell Research & Therapy,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: July 19, 2024
Abstract
Due
to
the
rapid
development
of
stem
cell
technology,
there
have
been
tremendous
advances
in
molecular
biological
and
pathological
research,
therapy
as
well
organoid
technologies
over
past
decades.
Advances
genome
editing
particularly
discovery
clustered
regularly
interspaced
short
palindromic
repeats
(CRISPR)
CRISPR-related
protein
9
(Cas9),
further
facilitated
researches.
The
CRISPR-Cas9
technology
now
goes
beyond
creating
single
gene
enable
inhibition
or
activation
endogenous
loci
by
fusing
inhibitory
(CRISPRi)
activating
(CRISPRa)
domains
with
deactivated
Cas9
proteins
(dCas9).
These
tools
utilized
genome-scale
CRISPRi/a
screen
recognize
hereditary
modifiers
that
are
synergistic
opposing
malady
mutations
an
orderly
fair
manner,
thereby
identifying
illness
mechanisms
discovering
novel
restorative
targets
accelerate
medicinal
investigation.
However,
application
this
technique
is
still
relatively
rare
research.
There
numerous
specialized
challenges
applying
large-scale
useful
genomics
approaches
differentiated
populations.
Here,
we
present
first
comprehensive
review
on
CRISPR-based
functional
screening
field
cells,
practical
considerations
implemented
a
range
scenarios,
exploration
insights
into
fates,
disease
treatments
models.
This
will
broadly
benefit
scientists,
engineers
medical
practitioners
areas
