Viruses,
Journal Year:
2024,
Volume and Issue:
17(1), P. 11 - 11
Published: Dec. 25, 2024
Cyclophilin
(Cyp)
inhibitors
are
of
clinical
interest
in
respect
to
their
antiviral
activities
the
context
many
viral
infections
including
chronic
hepatitis
B
and
C.
Cyps
a
group
enzymes
with
peptidyl-prolyl
isomerase
activity
(PPIase),
known
be
required
for
replication
diverse
viruses
C
(HBV
HCV).
Amongst
Cyp
family,
molecular
mechanisms
underlying
effects
CypA
have
been
investigated
detail,
but
potential
roles
other
less
well
studied
hepatitis.
Furthermore,
most
studies
investigating
role
did
not
investigate
therapeutic
inhibition
already-established
rather
performed
neo-infections.
Here,
we
genetically
silencing
on
persistent
HCV
HBV
infections.
We
confirm
CypD
knock
down
demonstrate
novel
CypG
CypH
replication.
show,
furthermore,
that
has
modest
reproducible
impact
cultured
human
hepatocytes.
Cells,
Journal Year:
2024,
Volume and Issue:
13(7), P. 648 - 648
Published: April 8, 2024
Neurodegenerative
diseases
are
chronic
conditions
occurring
when
neurons
die
in
specific
brain
regions
that
lead
to
loss
of
movement
or
cognitive
functions.
Despite
the
progress
understanding
mechanisms
this
pathology,
currently
no
cure
exists
treat
these
types
diseases:
for
some
them
only
help
is
alleviating
associated
symptoms.
Mitochondrial
dysfunction
has
been
shown
be
involved
pathogenesis
most
neurodegenerative
disorders.
The
fast
and
transient
permeability
mitochondria
(the
mitochondrial
transition,
mPT)
an
initial
step
mechanism
apoptotic
necrotic
cell
death,
which
acts
as
a
regulator
tissue
regeneration
postmitotic
it
leads
irreparable
cells
function.
In
study,
we
review
role
transition
neuronal
death
major
diseases,
covering
inductors
mPTP
opening
neurons,
including
ones—free
radicals
calcium—and
discuss
perspectives
difficulties
development
neuroprotective
strategy
based
on
inhibition
Microbiome,
Journal Year:
2025,
Volume and Issue:
13(1)
Published: Jan. 20, 2025
Alzheimer's
disease
(AD)
is
a
prevalent
neurodegenerative
(ND).
In
recent
years,
multiple
clinical
and
animal
studies
have
shown
that
mitochondrial
dysfunction
may
be
involved
in
the
pathogenesis
of
AD.
addition,
short-chain
fatty
acids
(SCFA)
produced
by
intestinal
microbiota
metabolism
been
considered
to
important
factors
affecting
central
nervous
system
(CNS)
homeostasis.
Among
main
mediators
host-microbe
interactions,
volatile
play
crucial
role.
Nevertheless,
influence
pathways
microorganisms
their
metabolites
on
remain
uncertain.
this
study,
we
present
distinctions
blood
fecal
SCFA
levels
composition
between
healthy
individuals
those
diagnosed
with
We
found
AD
patients
showed
decrease
abundance
Akkermansia
muciniphila
propionic
acid
both
blood.
order
further
reveal
effects
mechanisms
prevention,
systematically
explored
administration
model
mice
cultured
hippocampal
neuronal
cells.
Results
oral
propionate
supplementation
ameliorated
cognitive
impairment
mice.
Propionate
downregulated
fission
protein
(DRP1)
via
G-protein
coupled
receptor
41
(GPR41)
enhanced
PINK1/PARKIN-mediated
mitophagy
43
(GPR43)
pathophysiology
which
contribute
maintaining
homeostasis
vivo
vitro.
Administered
A.
before
onset
improved
cognition,
division
Taken
together,
our
results
demonstrate
its
metabolite
protect
against
AD-like
pathological
events
mouse
models
targeting
homeostasis,
making
them
promising
therapeutic
candidates
for
prevention
treatment
International Journal of Molecular Sciences,
Journal Year:
2025,
Volume and Issue:
26(3), P. 1207 - 1207
Published: Jan. 30, 2025
Nuclear
receptors
(NRs)
are
ligand-activated
transcription
factors
that
regulate
a
broad
array
of
biological
processes,
including
inflammation,
lipid
metabolism,
cell
proliferation,
and
apoptosis.
Among
the
diverse
family
NRs,
peroxisome
proliferator-activated
(PPARs),
estrogen
receptor
(ER),
liver
X
(LXR),
farnesoid
(FXR),
retinoid
(RXR),
aryl
hydrocarbon
(AhR)
have
garnered
significant
attention
for
their
roles
in
neurodegenerative
diseases,
particularly
Alzheimer’s
disease
(AD).
NRs
influence
pathophysiology
AD
through
mechanisms
such
as
modulation
amyloid-beta
(Aβ)
deposition,
regulation
inflammatory
pathways,
improvement
neuronal
function.
However,
dual
role
progression,
where
some
may
exacerbate
while
others
offer
therapeutic
potential,
presents
critical
challenge
application
treatment.
This
review
explores
functional
diversity
highlighting
involvement
AD-related
processes
discussing
prospects
NR-targeting
strategies.
Furthermore,
key
challenges,
necessity
precise
identification
beneficial
detailed
structural
analysis
molecular
dynamics
simulations,
further
investigation
NR
AD,
tau
pathology
autophagy,
also
discussed.
Collectively,
continued
research
is
essential
to
clarify
ultimately
facilitating
potential
use
diagnosis,
prevention,
treatment
AD.
Brain,
Journal Year:
2024,
Volume and Issue:
unknown
Published: July 13, 2024
Abstract
Mitochondrial
and
synaptic
dysfunction
are
pathological
features
of
brain
ageing
cognitive
decline.
Synaptic
mitochondria
vital
for
meeting
the
high
energy
demands
transmission.
However,
little
is
known
about
link
between
age-related
metabolic
changes
integrity
mitochondria.
To
this
end,
we
investigated
mechanisms
advanced
glycation
end
product
(AGE)-mediated
mitochondrial
stress
evaluated
strategies
to
eliminate
these
toxic
metabolites.
Using
aged
novel
transgenic
mice
overexpressing
neuronal
glyoxalase
1
(GLO1),
comprehensively
analysed
alterations
in
accumulation/build-up
AGEs
related
metabolites
association
AGE
levels
with
function.
We
demonstrated
first
time
that
an
early
major
target
metabolite
methylglyoxal
(MG),
a
precursor
AGEs.
MG/AGE-insulted
exhibit
deterioration
Such
accumulation
MG/AGEs
positively
correlated
perturbation
oxidative
brain.
Importantly,
clearance
AGE-related
by
enhancing
GLO1,
key
enzyme
detoxification
AGEs,
reduces
improves
function
AGE-challenged
mice.
Furthermore,
direct
effect
on
hippocampal
neurons
live
slices
as
ex
vivo
model
vitro
cultured
recording
long-term
potentiation
(LTP)
measuring
spontaneously
occurring
miniature
excitatory
postsynaptic
currents
(mEPSCs).
Neuronal
GLO1
rescues
deficits
AGE-induced
plasticity
transmission
full
recovery
decline
LTP
or
frequency
mEPSC.
These
studies
explored
crosstalk
relevant
particularly
susceptible
damage,
highlighting
central
importance
degeneration
Thus,
augmenting
scavenge
represents
therapeutic
approach
reduce
improve
learning
memory.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 5, 2025
Abstract
APOE4
is
the
leading
genetic
risk
factor
for
Alzheimer’s
disease,
and
chronic
stress
a
environmental
factor.
Studies
suggest
that
confers
vulnerability
to
behavioral
neuropathological
effects
of
stress,
representing
potential
mechanism
by
which
this
variant
accelerates
onset
progression.
Whether
how
-mediated
manifests
in
neurons
hippocampus,
brain
region
particularly
susceptible
pathology,
remains
unexplored.
Using
combination
vivo
vitro
experiments
humanized
APOE3
knockin
mice
primary
hippocampal
from
these
animals,
we
investigate
whether
sensitivity
glucocorticoids,
main
hormones.
We
find
major
hallmark
stress/glucocorticoid-induced
damage,
tau
pathology
(i.e.,
accumulation,
hyperphosphorylation,
spreading)
exacerbated
versus
mice.
Moreover,
animals
exhibit
underlying
mitochondrial
dysfunction
enhanced
glucocorticoid
receptor
activation
factors
likely
contribute
pathogenesis
both
presence
absence
stress/glucocorticoids.
Supporting
concept,
show
opening
permeability
transition
pore
drives
mice,
pharmacological
inhibition
protective
against
ApoE4-mediated
phosphorylation
spreading,
downstream
synapse
loss.
These
findings
shed
light
on
mechanisms
carriers
identify
as
therapeutic
target
ameliorating
population.
