Neuroactive Kynurenines as Pharmacological Targets: New Experimental Tools and Exciting Therapeutic Opportunities
Pharmacological Reviews,
Год журнала:
2024,
Номер
76(6), С. 978 - 1008
Опубликована: Сен. 20, 2024
Both
preclinical
and
clinical
studies
implicate
functional
impairments
of
several
neuroactive
metabolites
the
kynurenine
pathway
(KP),
major
degradative
cascade
essential
amino
acid
tryptophan
in
mammals,
pathophysiology
neurologic
psychiatric
diseases.
A
number
KP
enzymes,
such
as
2,3-dioxygenase
(TDO2),
indoleamine
2,3-dioxygenases
(IDO1
IDO2),
aminotransferases
(KATs),
3-monooxygenase
(KMO),
3-hydroxyanthranilic
oxygenase
(3-HAO),
quinolinic
phosphoribosyltransferase
(QPRT),
control
brain
metabolism
health
disease
are
therefore
increasingly
considered
to
be
promising
targets
for
treatment
disorders
nervous
system.
Understanding
distribution,
cellular
expression,
regulation
enzymes
is
critical
conceptualization
implementation
successful
therapeutic
strategies.
SIGNIFICANCE
STATEMENT:
Studies
have
implicated
Key
regulate
both
disease,
making
them
treating
these
disorders.
Therefore,
understanding
developing
effective
This
review
endeavors
describe
processes
detail.
Язык: Английский
Redefining Roles: A Paradigm Shift in Tryptophan–Kynurenine Metabolism for Innovative Clinical Applications
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(23), С. 12767 - 12767
Опубликована: Ноя. 27, 2024
The
tryptophan-kynurenine
(KYN)
pathway
has
long
been
recognized
for
its
essential
role
in
generating
metabolites
that
influence
various
physiological
processes.
Traditionally,
these
have
categorized
into
distinct,
often
opposing
groups,
such
as
pro-oxidant
versus
antioxidant,
excitotoxic/neurotoxic
neuroprotective.
This
dichotomous
framework
shaped
much
of
the
research
on
conditions
like
neurodegenerative
and
neuropsychiatric
disorders,
well
cancer,
where
metabolic
imbalances
are
a
key
feature.
effects
significantly
influenced
by
factors,
including
concentration
particular
cellular
milieu
which
they
generated.
A
molecule
acts
neuroprotective
at
low
concentrations
may
exhibit
neurotoxic
elevated
levels.
oxidative
equilibrium
surrounding
environment
can
alter
function
KYN
from
an
antioxidant
to
pro-oxidant.
narrative
review
offers
comprehensive
examination
analysis
contemporary
understanding
metabolites,
emphasizing
their
multifaceted
biological
functions
relevance
numerous
pathological
underscores
pressing
necessity
paradigm
shift
comprehension
metabolism.
Understanding
context-dependent
roles
is
vital
novel
therapies
Alzheimer's
disease,
multiple
sclerosis,
cancer.
Comprehensive
modulation,
balancing
inflammatory
signals
enzyme
regulation,
promising
avenues
targeted,
effective
treatments.
Язык: Английский
Gene Expression and Activity of Selected Antioxidant and DNA Repair Enzymes in the Prefrontal Cortex of Sheep as Affected by Kynurenic Acid
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(6), С. 2381 - 2381
Опубликована: Март 7, 2025
The
prefrontal
cortex
(PCx)
is
involved
in
many
higher-order
cognitive
processes,
including
decision
making,
reasoning,
personality
expression,
and
social
cognition.
These
functions
are
associated
with
high
energy
demand
the
production
of
harmful
oxygen
radicals.
Recent
studies
indicate
that
kynurenic
acid
(KYNA)
exerts
neuroprotective
effects,
largely
due
to
its
anti-inflammatory
antioxidant
properties.
To
further
evaluate
potential
this
compound,
we
tested
hypothesis
increasing
KYNA
levels
sheep
cerebroventricular
circulation
would
positively
affect
mRNA
expression
activity
selected
DNA
repair
enzymes
distal
part
brain,
i.e.,
PCx.
Anestrous
were
infused
intracerebroventricularly
a
series
two
doses:
lower
(4
×
5
μg/60
μL/30
min)
higher
25
at
30
min
intervals.
results
demonstrated
exerted
significant
dose-dependent
stimulatory
effects
on
superoxide
dismutase
2,
catalase,
glutathione
peroxidase
1
while
inhibiting
their
transcription
similar
manner.
In
addition,
was
also
found
dose-dependently
activate
base
excision
pathway,
as
determined
by
increased
transcript
glycosylases:
N-methylpurine
glycosylase,
thymine-DNA
8-oxoguanine
glycosylase-1,
apurinic/apyrimidinic
endonuclease
1.
efficiency
damaged
nucleobases,
such
εA,
εC
8-oxoG,
these
response
central
infusion.
findings
expand
knowledge
protective
factor
against
oxidative
stress
nervous
system.
Язык: Английский
Activation of BDNF–TrkB Signaling in Specific Structures of the Sheep Brain by Kynurenic Acid
Cells,
Год журнала:
2024,
Номер
13(23), С. 1928 - 1928
Опубликована: Ноя. 21, 2024
Fluctuations
in
kynurenic
acid
(KYNA)
and
brain-derived
neurotrophic
factor
(BDNF)
levels
the
brain
reflect
its
neurological
status.
The
aim
of
study
was
to
investigate
effect
transiently
elevated
KYNA
concentrations
cerebroventricular
circulation
on
expression
BDNF
high-affinity
tropomyosin-related
kinase
receptor
B
(TrkB)
specific
structures
sheep
brain.
Intracerebroventricularly
cannulated
anestrous
were
subjected
a
series
four
30
min
infusions
KYNA:
4
×
5
μg/60
μL/30
(KYNA20,
Язык: Английский