It
is
hard
to
overestimate
the
influence
of
endocannabinoid
signaling
(ECS)
system
on
central
nervous
(CNS)
function.
In
40
years
since
cannabinoids
were
found
trigger
specific
cell
cascades,
studies
ECS
continue
cause
amazement,
surprise,
and
confusion!
CB1
cannabinoid
receptors
are
expressed
widely
in
CNS
regulate
cell-cell
communication
via
effects
release
both
neurotransmitters
gliotransmitters.
CB2
difficult
detect
but
seem
"punch
above
their
weight"
as
compounds
targeting
these
have
significant
inflammatory
state
behavior.
Positive
negative
allosteric
modulators
for
been
identified
examined
preclinical
studies.
Concentrations
ligands,
N-arachidonoylethanolamine
2-arachidonoylglycerol
(2-AG),
regulated
by
a
combination
enzymatic
synthesis
degradation
inhibitors
processes
available
making
way
into
clinical
trials.
Importantly,
regulates
many
essential
brain
functions,
including
regulation
reward,
anxiety,
inflammation,
motor
control,
cellular
development.
While
field
cusp
discoveries
providing
impactful
therapeutic
insights
disorders,
there
still
much
be
learned
about
this
remarkable
versatile
modulatory
system.
Antioxidants,
Год журнала:
2021,
Номер
11(1), С. 8 - 8
Опубликована: Дек. 21, 2021
Oxidative
stress
has
been
implicated
in
the
etiology
and
pathobiology
of
various
neurodegenerative
diseases.
At
baseline,
cells
nervous
system
have
capability
to
regulate
genes
for
antioxidant
defenses
by
engaging
nuclear
factor
erythroid
2
(NFE2/NRF)-dependent
transcriptional
mechanisms,
a
number
strategies
proposed
activate
these
pathways
promote
neuroprotection.
Here,
we
briefly
review
biology
transcription
factors
NFE2/NRF
family
brain
provide
evidence
differential
cellular
localization
members
system.
We
then
discuss
findings
context
oxidative
observed
two
diseases,
Parkinson’s
disease
(PD)
amyotrophic
lateral
sclerosis
(ALS),
present
current
activating
NFE2/NRF-dependent
transcription.
Based
on
expression
restricted
populations
neurons
glia,
propose
that,
when
designing
engage
neuroprotection,
relative
contributions
neuronal
non-neuronal
cell
types
overall
state
tissue
should
be
considered,
as
well
which
greatest
intrinsic
capacity
producing
enzymes.
International Journal of Molecular Sciences,
Год журнала:
2021,
Номер
22(9), С. 4994 - 4994
Опубликована: Май 8, 2021
Accumulation
of
the
neuronal
presynaptic
protein
alpha-synuclein
within
proteinaceous
inclusions
represents
key
histophathological
hallmark
a
spectrum
neurodegenerative
disorders,
referred
to
by
umbrella
term
a-synucleinopathies.
Even
though
is
expressed
predominantly
in
neurons,
pathological
aggregates
are
also
found
glial
cells
brain.
In
Parkinson's
disease
and
dementia
with
Lewy
bodies,
accumulates
mainly
neurons
forming
bodies
neurites,
whereas
multiple
system
atrophy,
mostly
cytoplasmic
oligodendrocytes.
addition,
astrogliosis
microgliosis
synucleinopathy
brains,
both
astrocytes
microglia
internalize
contribute
spread
pathology.
The
mechanisms
underlying
accumulation
that
under
physiological
conditions
express
low
non-detectable
levels
an
area
intense
research.
Undoubtedly,
presence
aggregated
can
disrupt
function
general
neurodegeneration
through
numerous
pathways.
Herein,
we
summarize
current
knowledge
on
role
glia,
highlighting
contribution
neuron-glia
connectome
initiation
progression,
which
may
represent
potential
therapeutic
target
for
International Journal of Molecular Sciences,
Год журнала:
2022,
Номер
23(9), С. 4925 - 4925
Опубликована: Апрель 28, 2022
Sepsis
is
a
life-threatening
organ
dysfunction
caused
by
dysregulated
host
response
to
infection,
leaving
the
inflammation
process
without
proper
resolution,
leading
tissue
damage
and
possibly
sequelae.
The
central
nervous
system
(CNS)
one
of
first
regions
affected
peripheral
sepsis,
exposing
neurons
an
environment
oxidative
stress,
triggering
neuronal
apoptosis.
Sepsis-associated
encephalopathy
(SAE)
most
frequent
sepsis-associated
dysfunction,
with
symptoms
such
as
deliriums,
seizures,
coma,
linked
increased
mortality,
morbidity,
cognitive
disability.
However,
current
therapy
does
not
avoid
those
patients'
symptoms,
evidencing
search
for
more
optimal
approach.
Herein
we
focus
on
microglia
prominent
therapeutic
target
due
its
multiple
functions
maintaining
CNS
homeostasis
polarizing
capabilities,
stimulating
resolving
neuroinflammation
depending
stimuli.
Microglia
polarization
studies
involving
nerve
cell
preservation
in
diseases
or
aggravated
neuroinflammation,
but
potential
overlooked.
We
highlight
peroxisome
proliferator-activated
receptor
gamma
(PPARγ)
neuroprotective
properties,
role
interaction
nuclear
factor-κB
(NF-κB)
mitogen-activated
kinases
(MAPK),
making
PPARγ
molecular
sepsis-related
come.
ACS Chemical Neuroscience,
Год журнала:
2024,
Номер
15(2), С. 258 - 267
Опубликована: Янв. 5, 2024
Neuroinflammation
plays
an
important
role
in
the
pathogenesis
of
neurodegenerative
diseases,
and
interrupting
microglial-mediated
neuroinflammation
has
been
suggested
as
a
promising
strategy
to
delay
or
prevent
progression
neurodegeneration.
In
this
study,
we
investigated
effects
JE-133,
optically
active
isochroman-2H-chromene
conjugate
containing
1,3-disubstituted
isochroman
unit,
on
lipopolysaccharide
(LPS)-induced
microglial
underlying
mechanisms
both
vitro
vivo.
First,
JE-133
treatment
decreased
LPS-induced
overproduction
interleukin-1
beta
(IL-1β),
interleukin-6
(IL-6),
tumor
necrosis
factor-α
(TNF-α),
nitrite,
nitric
oxide
synthase
(iNOS)
BV2
cells.
Further
study
revealed
that
downregulated
phosphorylation
level
JAK/STAT
upregulated
protein
Nrf2/HO-1
LPS-stimulated
cells
verified
directly
bound
Keap1
by
pull-down
assay.
Next,
administration
also
inhibited
vivo,
indicated
reduced
CD11b
overexpressed
mRNA
pro-inflammatory
cytokine
TNF-α
hippocampus
LPS-injected
mice.
Moreover,
regulative
pathways
were
Taken
together,
our
for
first
time
reports
exhibits
inhibitory
against
which
might
be
associated
with
simultaneous
regulation
Nrf2
pathways.
Our
findings
may
provide
clues
discovery
effective
drug
leads/candidates
neuroinflammation-associated
Journal of Cellular and Molecular Medicine,
Год журнала:
2024,
Номер
28(12)
Опубликована: Июнь 1, 2024
Abstract
Parkinson
disease
(PD)
is
one
of
the
most
common
neurodegenerative
diseases
brain.
Of
note,
brain
renin‐angiotensin
system
(RAS)
intricate
in
PD
neuropathology
through
modulation
oxidative
stress,
mitochondrial
dysfunction
and
neuroinflammation.
Therefore,
RAS
by
angiotensin
receptor
blockers
(ARBs)
angiotensin‐converting
enzyme
inhibitors
(ACEIs)
may
be
effective
reducing
risk
neuropathology.
It
has
been
shown
that
all
components
including
peptides
enzymes
are
present
different
areas.
Brain
plays
a
critical
role
regulation
memory
cognitive
function,
controlling
central
blood
pressure.
However,
exaggerated
implicated
pathogenesis
PD.
Two
well‐known
pathways
recognized
including;
classical
pathway
which
mainly
mediated
AngII/AT1R
detrimental
effects.
Conversely,
non‐classical
mostly
ACE2/Ang1‐7/MASR
AngII/AT2R
beneficial
effects
against
Exaggerated
affects
viability
dopaminergic
neurons.
fundamental
mechanism
was
not
fully
elucidated.
Consequently,
purpose
this
review
to
disclose
mechanistic
In
addition,
we
try
revise
how
ACEIs
ARBs
can
developed
for
therapeutics
Antioxidants,
Год журнала:
2021,
Номер
10(11), С. 1649 - 1649
Опубликована: Окт. 20, 2021
Reactive
oxygen
species
(ROS)
are
signalling
molecules
used
to
regulate
cellular
metabolism
and
homeostasis.
However,
excessive
ROS
production
causes
oxidative
stress,
one
of
the
main
mechanisms
associated
with
origin
progression
neurodegenerative
disorders
such
as
Parkinson’s
disease.
NRF2
(Nuclear
Factor-Erythroid
2
Like
2)
is
a
transcription
factor
that
orchestrates
response
stress.
The
regulation
has
been
shown
be
promising
strategy
modulate
neurodegeneration
pathway
affected
in
patients
this
disease,
activation
neuroprotective
effects
preclinical
models,
demonstrating
therapeutic
potential
pathway.
In
review,
we
highlight
recent
advances
regarding
NRF2,
including
effect
Angiotensin
II
an
endogenous
molecule
able
stress
dopaminergic
neurons.
genes
regulated
downstream
activation,
special
focus
on
Kruppel
Factor
9
(KLF9)
factor,
provide
clues
about
involved
process
well
future
approaches.
Neural Regeneration Research,
Год журнала:
2022,
Номер
0(0), С. 0 - 0
Опубликована: Янв. 1, 2022
Use
of
glucagon-like
peptide-1
receptor
agonist
or
dipeptidyl
peptidase
4
inhibitor
has
been
shown
to
lower
the
incidence
Parkinson's
disease
in
patients
with
diabetes
mellitus.
Therefore,
using
these
two
treatments
may
help
treat
disease.
To
further
investigate
mechanisms
action
compounds,
we
established
a
model
by
treating
mice
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
and
then
subcutaneously
injected
them
exendin-4
linagliptin.
We
found
that
both
linagliptin
reversed
motor
dysfunction,
glial
activation,
dopaminergic
neuronal
death
this
model.
In
addition,
induced
microglial
polarization
anti-inflammatory
M2
phenotype
reduced
pro-inflammatory
cytokine
secretion.
Moreover,
vitro
experiments
showed
treatment
inhibited
activation
nucleotide-binding
oligomerization
domain-
leucine-rich-repeat-
pyrin-domain-containing
3/caspase-1/interleukin-1β
pathway
subsequent
pyroptosis
decreasing
production
reactive
oxygen
species.
These
findings
suggest
exert
neuroprotective
effects
attenuating
neuroinflammation
through
regulation
mouse
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
drugs
serve
as
novel
for
