Expert Opinion on Therapeutic Targets,
Journal Year:
2024,
Volume and Issue:
28(1-2), P. 67 - 82
Published: Feb. 1, 2024
Introduction
Kv1.3
is
the
main
voltage-gated
potassium
channel
of
leukocytes
from
both
innate
and
adaptive
immune
systems.
Channel
function
required
for
common
processes
such
as
Ca2+
signaling
but
also
cell-specific
events.
In
this
context,
alterations
in
are
associated
with
multiple
disorders.
Excessive
activity
correlates
numerous
autoimmune
diseases,
while
reduced
currents
result
increased
cancer
prevalence
immunodeficiencies.
Frontiers in Cellular Neuroscience,
Journal Year:
2021,
Volume and Issue:
15
Published: Sept. 14, 2021
Microglia
are
macrophages
that
reside
in
the
central
nervous
system
(CNS)
and
belong
to
innate
immune
system.
Moreover,
they
crucially
involved
CNS
development,
maturation,
aging;
further,
closely
associated
with
neurons.
In
normal
conditions,
microglia
remain
a
static
state.
Upon
trauma
or
lesion
occurrence,
can
be
activated
subsequently
polarized
into
pro-inflammatory
anti-inflammatory
phenotype.
The
phenotypic
transition
is
regulated
by
numerous
modulators.
This
review
focus
on
literature
regarding
modulators
signaling
pathways
regulating
microglial
transition,
which
rarely
mentioned
other
reviews.
Hence,
this
provides
molecular
insights
could
potential
therapeutic
target
for
neuroinflammation.
Pharmacological Reviews,
Journal Year:
2023,
Volume and Issue:
75(4), P. 758 - 788
Published: March 14, 2023
Parkinson9s
disease
(PD)
is
a
neurodegenerative
disorder
characterized
by
selective
loss
of
dopaminergic
neurons
in
the
substantia
nigra
pars
compacta
(SNpc)
region
midbrain.
The
results
subsequent
reduction
dopamine
striatum,
which
underlies
core
motor
symptoms
PD.
To
date,
there
are
no
effective
treatments
to
stop,
slow,
or
reverse
pathological
progression
neurodegeneration.
This
unfortunate
predicament
because
current
early
stages
understanding
biological
targets
and
pathways
involved
PD
pathogenesis.
Ion
channels
have
become
emerging
for
new
therapeutic
development
due
their
essential
roles
neuronal
function
neuroinflammation.
Potassium
most
prominent
ion
channel
family
been
shown
be
critically
important
pathology
modulating
excitability,
neurotransmitter
release,
synaptic
transmission,
In
this
review,
members
subfamilies
voltage-gated
K+
channels,
inward
rectifying
Ca2+-activated
potassium
described.
Evidence
role
these
aetiology
discussed
together
with
latest
views
on
related
mechanisms
potential
as
developing
neuroprotective
drugs
Significance
Statement
second
common
disorder,
featuring
progressive
degeneration
It
multifactorial
involving
multiple
risk
factors
complex
pathobiological
mechanisms.
Mounting
evidence
suggests
that
play
vital
pathogenesis
regulating
excitability
immune
cell
function.
Therefore,
they
"hot"
PD,
demonstrated
clinical
trials
drug
candidates
targeting
therapy.
Biomedicine & Pharmacotherapy,
Journal Year:
2024,
Volume and Issue:
175, P. 116651 - 116651
Published: April 30, 2024
Voltage-gated
potassium
channel
1.3
(Kv1.3)
has
emerged
as
a
pivotal
player
in
numerous
biological
processes
and
pathological
conditions,
sparking
considerable
interest
potential
therapeutic
target
across
various
diseases.
In
this
review,
we
present
comprehensive
examination
of
Kv1.3
channels,
highlighting
their
fundamental
characteristics
recent
advancements
utilizing
inhibitors
for
treating
autoimmune
disorders,
neuroinflammation,
cancers.
Notably,
is
prominently
expressed
immune
cells
implicated
responses
inflammation
associated
with
diseases
chronic
inflammatory
conditions.
Moreover,
its
aberrant
expression
certain
tumors
underscores
role
cancer
progression.
While
preclinical
studies
have
demonstrated
the
efficacy
inhibitors,
clinical
translation
remains
pending.
Molecular
imaging
techniques
offer
promising
avenues
tracking
assessing
efficacy,
thereby
facilitating
development
application.
Challenges
future
directions
inhibitor
research
are
also
discussed,
emphasizing
significant
targeting
strategy
spectrum
Science Signaling,
Journal Year:
2025,
Volume and Issue:
18(870)
Published: Jan. 21, 2025
Chronic
exposure
to
manganese
(Mn)
induces
manganism
and
has
been
widely
implicated
as
a
contributing
environmental
factor
Parkinson’s
disease
(PD),
featuring
notable
overlaps
between
the
two
in
motor
symptoms
clinical
hallmarks.
Here,
we
developed
an
adult
Drosophila
model
of
Mn
toxicity
that
recapitulated
key
parkinsonian
features,
spanning
behavioral
deficits,
neuronal
loss,
dysfunctions
lysosomes
mitochondria.
Metabolomics
analysis
brain
body
tissues
these
flies
at
early
stage
identified
systemic
changes
metabolism
biotin
(also
known
vitamin
B
7
)
Mn-treated
groups.
Biotinidase-deficient
showed
exacerbated
Mn-induced
neurotoxicity,
parkinsonism,
mitochondrial
dysfunction.
Supplementing
diet
wild-type
with
ameliorated
pathological
phenotypes
concurrent
Mn.
Biotin
supplementation
also
three
standard
fly
models
PD.
Furthermore,
supplementing
culture
media
human
induced
stem
cells
(iPSCs)
differentiated
midbrain
dopaminergic
neurons
protected
against
dysregulation,
cytotoxicity,
loss.
Last,
expression
genes
encoding
biotin-related
proteins
patients
PD
revealed
increased
amounts
transporters
substantia
nigra
compared
healthy
controls,
suggesting
potential
role
altered
Together,
our
findings
underlying
neurotoxicity
pathology
flies,
for
which
dietary
was
preventative.
International Journal of Molecular Sciences,
Journal Year:
2025,
Volume and Issue:
26(7), P. 3275 - 3275
Published: April 1, 2025
Neuroinflammation
is
a
complex
immune
response
triggered
by
brain
injury
or
pathological
stimuli,
and
highly
exacerbated
in
neurodegenerative
diseases.
It
plays
dual
role
the
central
nervous
system,
promoting
repair
acute
stages
while
aggravating
disease
progression
contributing
to
neuronal
loss,
synaptic
dysfunction,
glial
dysregulation
chronic
phases.
Inflammatory
responses
are
mainly
orchestrated
microglia
infiltrated
monocytes,
which,
when
dysregulated,
not
only
harm
existing
neurons,
but
also
impair
survival
differentiation
of
neural
stem
progenitor
cells
affected
regions.
Modulating
neuroinflammation
crucial
for
harnessing
its
protective
functions
minimizing
detrimental
effects.
Current
therapeutic
strategies
focus
on
fine-tuning
inflammatory
through
pharmacological
agents,
bioactive
molecules,
cell-based
therapies.
These
approaches
aim
restore
homeostasis,
support
neuroprotection,
promote
regeneration
various
neurological
disorders.
However,
animal
models
sometimes
fail
reproduce
human-specific
brain.
In
this
context,
stem-cell-derived
provide
powerful
tool
study
neuroinflammatory
mechanisms
patient-specific
physiologically
relevant
context.
facilitate
high-throughput
screening,
personalized
medicine,
development
targeted
therapies
addressing
limitations
traditional
models,
paving
way
more
effective
treatments.
International Journal of Molecular Sciences,
Journal Year:
2022,
Volume and Issue:
23(15), P. 8286 - 8286
Published: July 27, 2022
Radiation-induced
brain
injury
(RIBI)
after
radiotherapy
has
become
an
increasingly
important
factor
affecting
the
prognosis
of
patients
with
head
and
neck
tumor.
With
delivery
high
doses
radiation
to
tissue,
microglia
rapidly
transit
a
pro-inflammatory
phenotype,
upregulate
phagocytic
machinery,
reduce
release
neurotrophic
factors.
Persistently
activated
mediate
progression
chronic
neuroinflammation,
which
may
inhibit
neurogenesis
leading
occurrence
neurocognitive
disorders
at
advanced
stage
RIBI.
Fully
understanding
microglial
pathophysiology
cellular
molecular
mechanisms
irradiation
facilitate
development
novel
therapy
by
targeting
prevent
RIBI
subsequent
neurological
neuropsychiatric
disorders.
