Translational Neurodegeneration,
Journal Year:
2024,
Volume and Issue:
13(1)
Published: Dec. 23, 2024
Abstract
Inflammasomes
represent
a
crucial
component
of
the
innate
immune
system,
which
respond
to
threats
by
recognizing
different
molecules.
These
are
known
as
pathogen-associated
molecular
patterns
(PAMPs)
or
host-derived
damage-associated
(DAMPs).
In
neurodegenerative
diseases
and
neuroinflammation,
accumulation
misfolded
proteins,
such
beta-amyloid
alpha-synuclein,
can
lead
inflammasome
activation,
resulting
in
release
interleukin
(IL)-1β
IL-18.
This
activation
also
induces
pyroptosis,
inflammatory
mediators,
exacerbates
neuroinflammation.
Increasing
evidence
suggests
that
inflammasomes
play
pivotal
role
diseases.
Therefore,
elucidating
investigating
regulation
these
is
paramount
importance.
review
primarily
focused
on
indicating
activated
through
canonical
pathway
potential
targets
for
treating
discussed.
FEBS Journal,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 12, 2025
Zika
virus
(ZIKV)
poses
a
significant
threat
due
to
its
association
with
severe
neurological
complications,
particularly
during
pregnancy.
Although
viruses
exhibit
tropism
for
neural
cells,
including
astrocytes,
the
role
of
these
cells
in
controlling
ZIKV
replication
remains
unclear.
In
this
study,
we
demonstrated
that
induces
caspase‐1
activation
primary
astrocytes
despite
absence
classical
signs
inflammasome
activation.
Caspase‐1
and
caspase‐11
double
knockout
(
caspase‐1/11
−/−
)
heightened
permissiveness
viral
replication,
accompanied
by
overactivation
glycolytic
metabolism.
Inhibition
glycolysis
reversed
susceptibility
infection.
Protein
network
analysis
revealed
mammalian
target
rapamycin
complex
(mTORC)
as
link
between
proteins
involved
caspase‐1,
mTORC
inhibition
also
suppressed
replication.
Furthermore,
found
impact
on
depends
regulation
pyruvate
transport
mitochondria
Overall,
our
findings
elucidate
caspase‐1/11‐dependent
microbicidal
mechanism
involves
mTORC/glycolytic
pathway/pyruvate
axis,
providing
insights
into
potential
therapeutic
targets
Cells,
Journal Year:
2025,
Volume and Issue:
14(7), P. 487 - 487
Published: March 24, 2025
Chronic
pain
is
a
widespread
global
health
problem
with
profound
socioeconomic
implications,
affecting
millions
of
people
all
ages.
Glial
cells
(GCs)
in
pathways
play
essential
roles
the
processing
signals.
Dysregulation
GC
activity
contributes
to
chronic
states,
making
them
targets
for
therapeutic
interventions.
Non-pharmacological
approaches,
such
as
exercise,
are
strongly
recommended
effective
management.
This
review
examines
link
between
regular
physical
(PA),
and
glial
cell-mediated
processing,
highlighting
its
potential
strategy
managing
pain.
Exercise
not
only
improves
overall
quality
life
but
also
influences
function
GCs.
Recent
research
highlights
ability
exercise
mitigate
neuroinflammatory
responses
modulate
GCs
by
reducing
activation
microglia
astrocytes,
well
modulating
expression
biomarkers,
thereby
attenuating
hypersensitivity.
Here,
we
summarize
new
insights
into
role
non-pharmacological
intervention
relief
Journal of the American Heart Association,
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 10, 2025
Background
Post‐stroke
depression
(PSD)
is
a
prevalent
neuropsychiatric
complication
of
stroke.
However,
the
mechanisms
underlying
PSD
are
still
unclear.
Here,
we
aimed
to
investigate
role
HCN1
(hyperpolarization‐activated
cyclic
nucleotide‐gated
cation
channel
1)
in
pathogenesis
and
its
mechanisms.
Methods
The
mice
model
was
established
by
middle
cerebral
artery
occlusion
vivo.
Four
weeks
after
occlusion,
anxiety‐
depression‐like
behaviors
were
evaluated
various
behavioral
tests.
HCN
channels
downregulated
pharmacological
inhibitor
or
neuron‐specific
adeno‐associated
virus.
oxygen–glucose
deprivation/reoxygenation
SY5Y
cells
used
study
vitro.
Results
Mice
exhibited
behavior
4
along
with
significant
increase
protein
expression
ischemic
hippocampus.
Furthermore,
I
h
current
on
neurons
hippocampus
notably
enhanced,
whereas
neuronal
excitability
decreased
mice.
Treatment
selective
ZD7288
protected
against
injury
suppressing
K
+
efflux.
Additionally,
observed
expressions
NLRP3
(nucleotide‐binding
domain‐like
receptor
3)
inflammasome
pathway‐related
molecules
Knockdown
via
virus
injection
into
resulted
inflammasome‐related
improvement
Conclusions
Downregulation
has
beneficial
effect
pathway,
thus
offering
promise
as
strategy
for
preventing
treating
PSD.
Viruses,
Journal Year:
2025,
Volume and Issue:
17(4), P. 572 - 572
Published: April 16, 2025
Despite
the
success
of
antiretroviral
therapy
(ART)
in
suppressing
viral
replication
blood,
HIV
persists
central
nervous
system
(CNS)
and
causes
chronic
neurocognitive
impairment,
a
hallmark
HIV-associated
disorders
(HAND).
This
review
looks
at
complex
interactions
among
HIV,
blood–brain
barrier
(BBB),
neuroinflammation,
roles
proteins,
immune
cell
trafficking,
pro-inflammatory
mediators
establishing
maintaining
latent
reservoirs
CNS,
particularly
microglia
astrocytes.
Key
findings
show
disruption
BBB,
monocyte
infiltration,
activation
CNS-resident
cells
by
proteins
like
Tat
gp120,
contributing
to
neuroinflammatory
environment
neuronal
damage.
Advances
epigenetic
regulation
latency
have
identified
targets
histone
modifications
DNA
methylation,
new
therapeutic
strategies
latency-reversing
agents
(LRAs),
gene
editing
(CRISPR/Cas9),
nanoparticle-based
drug
delivery
also
offer
hope.
While
we
made
significant
progress
understanding
molecular
basis
persistence
overcoming
challenges
BBB
penetration
neuroinflammation
is
key
developing
effective
therapies.
Further
research
into
combination
therapies
novel
systems
will
help
improve
outcomes
for
HAND
patients
bring
us
closer
functional
cure
HIV.
Journal of Parkinson s Disease,
Journal Year:
2024,
Volume and Issue:
unknown, P. 1 - 29
Published: Sept. 25, 2024
Increasing
evidence
suggests
a
potential
role
for
infectious
pathogens
in
the
etiology
of
synucleinopathies,
group
age-related
neurodegenerative
disorders
including
Parkinson’s
disease
(PD),
multiple
system
atrophy
and
dementia
with
Lewy
bodies.
In
this
review,
we
discuss
link
between
infections
synucleinopathies
from
historical
perspective,
present
emerging
that
supports
link,
address
current
research
challenges
focus
on
neuroinflammation.
Infectious
can
elicit
neuroinflammatory
response
modulate
genetic
risk
PD
related
synucleinopathies.
The
mechanisms
how
might
be
linked
as
well
overlap
immune
cellular
pathways
affected
by
virulent
disease-related
factors
are
discussed.
Here,
an
important
α-synuclein
against
is
emerging.
Critical
methodological
knowledge
gaps
addressed,
provide
new
future
perspectives
to
these
gaps.
Understanding
neuroinflammation
influence
will
essential
development
early
diagnostic
tools
novel
therapies.
Journal of Medicinal Chemistry,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 22, 2024
Activation
of
the
NLRP3
inflammasome
in
response
to
danger
signals
is
a
key
innate
immune
mechanism
and
results
production
pro-inflammatory
cytokines
interleukin-1β
(IL-1β)
interleukin-18
(IL-18)
as
well
pyroptotic
cell
death.
Aberrant
activation
has
been
linked
many
acute
chronic
conditions
ranging
from
atherosclerosis
Alzheimer's
disease
cancer,
based
on
clinical
success
IL-1-targeting
therapies,
emerged
an
attractive
therapeutic
target.
Herein
we
describe
our
discovery,
characterization,
structure-based
optimization
pyridazine-based
series
inhibitors
initiating
high-throughput
screening
campaign.
The
scaffold,
exemplified
by
lead
molecule
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(18), P. 10034 - 10034
Published: Sept. 18, 2024
This
study
investigated
the
neuroprotective
effects
of
peripheral
nerve
microcurrent
stimulation
therapy
in
a
rat
model
middle
cerebral
artery
occlusion
(MCAO).
Twenty
8-week-old
male
Sprague
Dawley
rats
weighing
300–330
g
were
categorised
into
group
A,
serving
as
healthy
control;
B,
including
subjected
to
MCAO;
C,
receiving
immediately
after
MCAO,
which
was
continued
for
one
week;
and
D,
week
before
MCAO.
A
gross
morphological
analysis,
behavioural
motion
histological
examination,
immunohistochemistry,
Western
blotting
conducted.
Microcurrent
significantly
reduced
ischaemic
damage
pyramidal
cells
hippocampus
CA1
region.
Haematoxylin
eosin
staining
revealed
infarction
areas/viable
cell
numbers
0%/94.33,
28.53%/40.05,
17.32%/80.13,
5.38%/91.34
groups
respectively
(p
<
0.001).
analysis
that
total
distances
moved
1945.24
cm,
767.85
1781.77
2122.22
cm
0.05),
mean
speeds
6.48
cm/s,
2.50
5.43
6.82
0.05).
Inflammatory
markers
(cluster
differentiation
68,
interleukin-6,
tumour
necrosis
factor-α)
decreased
treated
proinflammatory,
oxidative
stress,
apoptosis-related
protein
levels,
along
with
increased
angiogenic
factors
mitogen-activated
kinase
(MAPK)
pathway
modulation
groups.
Peripheral
effectively
mitigates
damage,
promotes
recovery,
reduces
inflammation,
modulates
expression,
emphasising
its
potential
therapeutic
strategy
stroke.
