Progress in Neurobiology,
Год журнала:
2017,
Номер
160, С. 82 - 100
Опубликована: Окт. 31, 2017
Multiple
sclerosis
is
the
most
common
inflammatory
demyelinating
disease
of
central
nervous
system,
caused
by
an
autoimmune
response
against
myelin
that
eventually
leads
to
progressive
neurodegeneration
and
disability.
Although
knowledge
on
its
underlying
neurobiological
mechanisms
has
considerably
improved,
there
a
still
unmet
need
for
new
treatment
options,
especially
forms
disease.
Both
preclinical
clinical
data
suggest
cannabinoids,
derived
from
Cannabis
sativa
plant,
may
be
used
control
symptoms
such
as
spasticity
chronic
pain,
whereas
only
indicate
these
compounds
their
endogenous
counterparts,
i.e.
endocannabinoids,
also
exert
neuroprotective
effects
slow
down
progression.
Here,
we
review
studies
could
explain
therapeutic
action
cannabinoid-based
medicines,
well
medical
potential
modulating
endocannabinoid
signaling
in
multiple
sclerosis,
with
link
other
neuroinflammatory
disorders
share
hallmarks
pathogenetic
features.
International Journal of Molecular Sciences,
Год журнала:
2018,
Номер
19(3), С. 833 - 833
Опубликована: Март 13, 2018
The
biological
effects
of
cannabinoids,
the
major
constituents
ancient
medicinal
plant
Cannabis
sativa
(marijuana)
are
mediated
by
two
members
G-protein
coupled
receptor
family,
cannabinoid
receptors
1
(CB1R)
and
2.
CB1R
is
prominent
subtype
in
central
nervous
system
(CNS)
has
drawn
great
attention
as
a
potential
therapeutic
avenue
several
pathological
conditions,
including
neuropsychological
disorders
neurodegenerative
diseases.
Furthermore,
cannabinoids
also
modulate
signal
transduction
pathways
exert
profound
at
peripheral
sites.
Although
have
potential,
their
psychoactive
largely
limited
use
clinical
practice.
In
this
review,
we
briefly
summarized
our
knowledge
endocannabinoid
system,
focusing
on
CNS,
with
emphasis
recent
breakthroughs
field.
We
aim
to
define
roles
modulation
signaling
association
pathophysiological
conditions.
believe
that
significance
masked
adverse
here
alternative
strategies
discussed
take
advantage
cannabinoids.
Frontiers in Immunology,
Год журнала:
2018,
Номер
9
Опубликована: Янв. 29, 2018
Inflammation
is
an
immune
response
that
works
as
a
contained
fire
pre-emptively
sparked
defensive
process
during
infections
or
upon
any
kind
of
tissue
insult,
and
spontaneously
extinguished
after
elimination
termination
the
damage.
However,
persistent
uncontrolled
reactions
act
wildfire
promote
chronic
inflammation,
unresolved
damage
and,
eventually,
diseases.
A
wide
network
soluble
mediators,
among
which
endogenous
bioactive
lipids,
governs
all
processes.
They
are
secreted
by
basically
cells
involved
in
inflammatory
processes
constitute
crucial
infrastructure
trigger,
coordinate
confine
mechanisms.
these
molecules
also
deeply
detrimental
transition
from
to
be
it
for
excessive
action
pro-inflammatory
lipids
impairment
functions
carried
out
resolving
ones.
As
matter
fact,
have
been
linked,
date,
several
diseases,
including
rheumatoid
arthritis,
atherosclerosis,
diabetes,
cancer,
bowel
disease,
lupus
multiple
sclerosis.
This
review
summarizes
current
knowledge
on
involvement
main
classes
–
namely
classical
eicosanoids,
pro-resolving
lipid
lysoglycerophospholipids/sphingolipids
endocannabinoids
cellular
molecular
mechanisms
lead
pathogenesis
disorders.
Pharmacological Reviews,
Год журнала:
2017,
Номер
70(1), С. 12 - 38
Опубликована: Дек. 7, 2017
Classically,
polyunsaturated
fatty
acids
(PUFA)
were
largely
thought
to
be
relatively
inert
structural
components
of
brain,
important
for
the
formation
cellular
membranes.
Over
past
10
years,
a
host
bioactive
lipid
mediators
that
are
enzymatically
derived
from
arachidonic
acid,
main
n-6
PUFA,
and
docosahexaenoic
n-3
PUFA
in
known
regulate
peripheral
immune
function,
have
been
detected
brain
shown
microglia
activation.
Recent
advances
focused
on
how
molecular
signaling
microglia,
especially
context
neuroinflammation
behavior.
Several
active
drugs
provide
proof
concept
targeting
brain.
Because
metabolism
relies
complex
integration
diet,
metabolism,
including
liver
blood,
which
supply
with
PUFAs
can
altered
by
genetics,
sex,
aging,
there
many
pathways
disrupted,
leading
homeostasis.
Brain
neurologic
disorders
may
viable
targets
development
novel
therapeutics.
In
this
study,
we
discuss
particular
their
metabolites
phenotype
function
exert
anti-inflammatory
proresolving
activities
Frontiers in Cellular Neuroscience,
Год журнала:
2017,
Номер
10
Опубликована: Янв. 3, 2017
The
identification
and
cloning
of
the
two
major
cannabinoid
(CB¬1
CB2)
receptors
together
with
discovery
their
endogenous
ligands
in
late
80s
early
90s,
resulted
a
effort
aimed
at
understanding
mechanisms
physiological
roles
endocannabinoid
system
(ECS).
Due
to
its
expression
localization
central
nervous
(CNS),
CB1
receptor
(endocannabinoids)
enzymes
involved
synthesis
degradation,
has
been
implicated
multiple
pathophysiological
events
ranging
from
memory
deficits
neurodegenerative
disorders
among
others.
In
this
review,
we
will
provide
general
overview
emphasis
on
health
disease.
We
describe
our
current
complex
aspects
signaling
trafficking,
including
non-canonical
pathways
such
as
those
mediated
by
β-arrestins
within
context
functional
selectivity
ligand
bias.
Finally,
highlight
some
which
have
implicated.
Significant
knowledge
achieved
over
last
30
years.
However,
much
more
research
is
still
needed
fully
understand
system,
particularly
vivo,
unlock
true
potential
source
therapeutic
targets.
Current Drug Metabolism,
Год журнала:
2016,
Номер
17(3), С. 206 - 226
Опубликована: Янв. 21, 2016
This
review
consists
of
three
parts,
representing
different
possibilities
interactions
between
cannabinoid
receptor
ligands
both
exogenous
and
endogenous
origin
cytochrome
P450
enzymes
(CYPs).
The
first
part
deals
with
cannabinoids
as
CYP
substrates,
the
second
summarizes
current
knowledge
on
influence
various
metabolic
activity
CYP,
third
outline
a
possible
involvement
endocannabinoid
system
in
regulation
liver
activity.We
performed
structured
search
bibliographic
drug
databases
for
peer-reviewed
literature
using
focused
questions.Biotransformation
via
hydrolytic
pathway
is
major
route
metabolism
deactivation
substrates
characteristic,
contrast
to
minor
oxidative
involved
bioactivation
reactions.
Phytocannabinoids
are
extensively
metabolized
by
CYPs.
CYP2C9,
CYP2C19,
CYP3A4
catalyze
most
their
hydroxylations.
Similarly,
represents
synthetic
used
therapeutically
drugs
that
abused.
In
vitro
experiments
document
mostly
inhibitory
phytocannabinoids,
cannabidiol
potent
inhibitor
many
drug-drug
at
level
reported,
but
clinical
relevance
remains
unclear.
direct
activation/inhibition
nuclear
receptors
cells
may
result
change
expression
activity.
Finally,
we
hypothesize
interplay
central
numerous
nervous
systems,
resulting
hormone-mediated
signal
towards
hepatocytes.
