Drug Design Development and Therapy,
Journal Year:
2024,
Volume and Issue:
Volume 18, P. 6145 - 6164
Published: Dec. 1, 2024
This
review
elucidates
the
pivotal
role
of
pyroptosis,
triggered
by
gut
microbiota,
in
development
multiple
sclerosis
(MS),
emphasizing
its
significance
within
gut-brain
axis.
Our
comprehensive
analysis
recent
literature
reveals
how
dysbiosis
microbiota
MS
patients-characterized
reduced
microbial
diversity
and
shifts
bacterial
populations-profoundly
impacts
immune
regulation
integrity
central
nervous
system
(CNS).
Pyroptosis,
an
inflammatory
form
programmed
cell
death,
significantly
exacerbates
promoting
release
cytokines
causing
substantial
damage
to
CNS
tissues.
The
facilitates
this
detrimental
process
through
metabolites
such
as
short-chain
fatty
acids
neuroactive
compounds,
or
self-structural
products
like
lipopolysaccharides
(LPS),
which
modulate
responses
influence
neuronal
survival.
highlights
potential
modulating
regulate
thereby
suggesting
that
targeting
pathway
could
be
a
promising
therapeutic
strategy
mitigate
preserve
patients
with
MS.
Biomedicine & Pharmacotherapy,
Journal Year:
2024,
Volume and Issue:
177, P. 117009 - 117009
Published: June 21, 2024
Cyclic
adenosine
monophosphate
(cAMP)
is
a
key
second
messenger
that
regulates
signal
transduction
pathways
pivotal
for
numerous
biological
functions.
Intracellular
cAMP
levels
are
spatiotemporally
regulated
by
their
hydrolyzing
enzymes
called
phosphodiesterases
(PDEs).
It
has
been
shown
increased
in
the
central
nervous
system
(CNS)
promote
neuroplasticity,
neurotransmission,
neuronal
survival,
and
myelination
while
suppressing
neuroinflammation.
Thus,
elevating
through
PDE
inhibition
provides
therapeutic
approach
multiple
CNS
disorders,
including
sclerosis,
stroke,
spinal
cord
injury,
amyotrophic
lateral
traumatic
brain
Alzheimer's
disease.
In
particular,
of
cAMP-specific
PDE4
subfamily
widely
studied
because
its
high
expression
CNS.
So
far,
clinical
translation
full
inhibitors
hampered
dose-limiting
side
effects.
Hence,
focusing
on
signaling
cascades
downstream
activated
upon
presents
promising
strategy,
offering
novel
pharmacologically
safe
targets
treating
disorders.
Yet,
underlying
PDE(4)
remain
partially
elusive.
This
review
comprehensive
overview
existing
knowledge
regarding
mediators
induced
or
stimulators.
Furthermore,
we
highlight
gaps
future
perspectives
may
incentivize
additional
research
concerning
inhibition,
thereby
providing
approaches
Multiple Sclerosis and Related Disorders,
Journal Year:
2025,
Volume and Issue:
94, P. 106276 - 106276
Published: Jan. 18, 2025
A
recent
application
of
the
GRADE
guidelines
indicated
Faremus,
a
5-day
neuromodulation
for
15
min
per
day
via
transcranial
direct
current
stimulation
(tDCS),
as
medium
to
highly
recommendable
alleviating
fatigue
in
multiple
sclerosis
(MS).
With
this
pilot
study
we
aimed
evaluate
feasibility,
acceptance,
safety,
and
effectiveness
Faremus
treatment
carried
out
multicenter
context.
The
Rome
unit
prepared
intervention,
supplied
personalized
electrodes
San
Martino
Hospital
Genova,
where
neurological
team
enrolled
population
fatigued
people
with
(PwMS)
treatment.
All
17
patients
completed
treatment,
reporting
optimal
acceptance
safety
when
using
setting.
involved,
including
neurologists,
neurophysiopathology
technicians,
engineers,
physicists,
psychologists
expressed
high
appreciation
(average
score
8
10).
improved
symptoms
by
an
average
27%,
levels
comparable
previous
studies.
Similarly,
mild
depressive
38%.
electroceutical
anodal
tDCS
over
bilateral
whole-body
somatosensory
cortex
occipital
cathode,
is
well
accepted
can
be
applied
feasibly,
safely
effectively
setting,
offering
reliable
tool
relieve
fatigue-related
symptoms,
thus
supporting
quality
life
MS.
present
lays
starting
point
involvement
MS
units
nationwide
therapeutic
enrichment
their
patients.
ACS Chemical Neuroscience,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 17, 2025
Cerebral
dysfunctions
give
rise
to
a
wide
range
of
neurological
diseases
due
the
structural
and
functional
complexity
human
brain
stemming
from
interactive
cellular
metabolism
its
specific
cells,
including
neurons
glial
cells.
In
parallel
with
advances
in
isolation
measurement
technologies,
genome-scale
metabolic
models
(GEMs)
have
become
powerful
tool
studies
systems
biology
provide
critical
insights
into
understanding
sophisticated
eukaryotic
systems.
this
study,
cell-specific
GEMs
were
reconstructed
for
neurons,
astrocytes,
microglia,
oligodendrocytes,
oligodendrocyte
precursor
cells
by
integrating
single-cell
RNA-seq
data
global
Human1
via
task-driven
integrative
network
inference
tissues
(tINIT)
algorithm.
Then,
intercellular
reactions
among
oligodendrocytes
added
generate
combined
model,
iHumanBrain2690.
This
was
used
prediction
alterations
glucose,
ketone
bodies,
oxygen
change,
reporter
metabolites.
Glucose
supplementation
increased
subsystems'
activities
glycolysis,
bodies
elevated
those
TCA
cycle
oxidative
phosphorylation.
Reporter
metabolite
analysis
identified
L-carnitine
arachidonate
as
top
metabolites
gray
white
matter
microglia
multiple
sclerosis
(MS),
respectively.
Carbamoyl-phosphate
found
be
primary
progressive
MS.
Taken
together,
single
integrated
iHumanBrain2690
networks
help
us
elucidate
complex
physiology
homeostasis
health
disease.
Neural Regeneration Research,
Journal Year:
2023,
Volume and Issue:
19(7), P. 1437 - 1445
Published: Nov. 8, 2023
Currently,
there
is
a
lack
of
effective
medicines
capable
halting
or
reversing
the
progression
neurodegenerative
disorders,
including
amyotrophic
lateral
sclerosis,
Parkinson's
disease,
multiple
Alzheimer's
disease.
Given
unmet
medical
need,
it
necessary
to
reevaluate
existing
paradigms
how
target
these
diseases.
When
considering
diseases
from
systemic
neurometabolic
perspective,
becomes
possible
explain
shared
pathological
features.
This
innovative
approach
presented
in
this
paper
draws
upon
extensive
research
conducted
by
authors
and
researchers
worldwide.
In
review,
we
highlight
importance
metabolic
mitochondrial
dysfunction
context
We
provide
an
overview
risk
factors
associated
with
developing
genetic,
epigenetic,
environmental
factors.
Additionally,
examine
mechanisms
implicated
such
as
oxidative
stress,
accumulation
misfolded
proteins,
inflammation,
demyelination,
death
neurons,
insulin
resistance,
dysbiosis,
neurotransmitter
disturbances.
Finally,
outline
proposal
for
restoration
metabolism,
crucial
aspect
that
may
hold
key
facilitating
curative
therapeutic
interventions
disorders
forthcoming
advancements.
