Folia Pharmacologica Japonica,
Год журнала:
2024,
Номер
160(1), С. 19 - 22
Опубликована: Дек. 31, 2024
Glaucoma
is
an
age-related
neurodegenerative
disease
and
the
leading
cause
of
blindness,
but
currently
no
fundamental
treatment
has
been
present.
The
main
to
reduce
intraocular
pressure,
which
expected
delay
progression
disease.
However,
there
are
many
glaucoma
patients
for
whom
cannot
be
controlled
by
lowering
pressure
alone,
development
a
required.
Meanwhile,
clinical
application
gene
therapy
increasing
worldwide.
Various
vectors
still
being
developed,
technological
change
much
faster
in
this
field.
Gene
already
clinically
applied
several
diseases,
not
yet
established.
Our
group
investigating
new
using
neurotrophic
factor
signaling.
And
we
aim
only
suppress
neuroprotection,
also
recover
visual
function
axonal
regeneration.
Phytotherapy Research,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 4, 2025
ABSTRACT
Drugs
generally
used
in
major
depressive
disorder
are
considered
inappropriate
for
the
more
common
milder
forms.
The
efficacy
of
saffron
extracts
has
been
demonstrated
mild
to
moderate
depression
and
preclinical
models
depression.
However,
evidence
activity
on
reduced
hedonic
responsiveness
motivational
anhedonia
is
limited.
Since
dopamine
transmission
dysfunctions
crucially
involved
seems
positively
modulate
release,
we
studied
potential
antidepressant
anti‐anhedonic
effects
a
standardized
formulation
extract
anhedonia‐like
behaviors,
patients
diagnosed
with
unipolar
or
bipolar
We
tested
rat
model
stress‐induced
using
sucrose
self‐administration
protocols
investigated
molecular
underpinnings
this
effect
focusing
DARPP‐32
phosphorylation
pattern
response
reinforcer
BDNF–TrkB
signaling,
nucleus
accumbens
medial
prefrontal
cortex.
In
parallel,
pilot
double‐blind
placebo‐controlled
study
whether
add‐on
therapy
symptoms
anhedonia,
measured
by
Montgomery–Åsberg
Depression
Rating
Scale.
Repeated
administration
restored
motivation
reactivity
reward‐associated
cues
anhedonic
rats,
likely
modulating
dopaminergic
signaling.
depressed
patients,
an
8‐week
induced
global
improvement
significant
reduction
anhedonia.
supports
pro‐motivational
suggests
potentially
useful
saffron‐based
augmentation
strategy
albeit
limitations
due
small
sample
size
short
trial
duration.
Zusammenfassung
Hintergrund
Neue
antidepressive
Substanzen
stellen
die
Erklärungsansätze
zu
Wirkmechanismen
der
traditionellen
Psychopharmakologie
vor
Herausforderungen.
Fragestellung
Was
könnten
gemeinsame
Effekte
verschiedenen
Antidepressiva
sein
und
welche
Rolle
spielen
dabei
jeweils
extrapharmakologische
Faktoren
wie
Körper
Umwelt?
Material
Methode
Die
verfügbare
Literatur
über
klinische
präklinische
Daten
vermuteten
gemeinsamen
Wirkfaktoren
von
serotonergen
Psychedelika,
(Es‑)Ketamin,
monoaminergen
Zuranolon
wird
dargestellt
Einfluss
Kontextfaktoren
auf
jeweiligen
diskutiert.
Ergebnisse
Es
deutet
vieles
darauf
hin,
dass
klassischere
neuere
pharmakologische
Ansätze
Depressionsbehandlung
ähnliche
teilen
könnten.
Diese
Mechanismen
begünstigen
langfristige
Neuroplastizität,
nachgeschaltete
molekulare
Kaskaden
auslösen
können
vice
versa.
Darüber
hinaus
wurde
für
meisten
antidepressiven
auch
eine
Verbesserung
negativen
Verzerrung
in
emotionalen
Verarbeitung
nachgewiesen.
Der
extrapharmakologischer
scheint
notwendig
sein,
damit
biopsychologischen
Veränderungen
antidepressiv
wirksam
können.
Schlussfolgerungen
Anstatt
Umwelt,
soziale
Interaktionen
den
Placeboeffekten
zählen,
sollten
sie
als
essenzieller
Baustein
Wirkung
geprüft
klinischen
Versorgung
mitbedacht
werden.
Molecular Psychiatry,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 31, 2025
Most
of
the
fear
literature
on
humans
and
animals
tests
healthy
individuals.
However,
memories
can
differ
between
individuals
those
previously
exposed
to
traumatic
stress,
such
as
a
car
accident,
sexual
abuse,
military
combat
personal
assault.
Traumatic
stress
lead
post-traumatic
disorder
(PTSD)
which
presents
alterations
in
memories,
an
impairment
extinction
recall.
PTSD-like
animal
models
are
single
highly
stressful
experience
laboratory,
immobilization
or
single-prolonged
stress.
Some
days
later,
model
be
tested
procedures
that
help
uncover
molecular
mechanisms
memories.
In
this
review,
there
discussed
stress-induced
patients
with
PTSD
models.
The
focus
is
effects
estradiol
cortisol/corticosterone
hormones
different
genes,
FKBP
prolyl
isomerase
5
gene
(FKBP5)
-
FK506
binding
protein
51
(FKBP51),
pituitary
adenylate
cyclase-activating
peptide
(PACAP)
polypeptide
type
I
receptor
(PAC1R),
endocannabinoid
(eCB)
system
tropomyosin
kinase
B
(TrkB)
brain-derived
neurotrophic
factor
(BDNF).
conclusion
greater
emphasis
should
placed
investigating
PTSD,
through
direct
testing
use
relevant
Cells,
Год журнала:
2025,
Номер
14(7), С. 476 - 476
Опубликована: Март 22, 2025
Brain-derived
neurotrophic
factor
(BDNF)
is
an
important
neuromodulator
of
nervous
system
functions
and
plays
a
key
role
in
neuronal
growth
survival,
neurotransmission,
synaptic
plasticity.
The
effects
BDNF
are
mainly
mediated
by
the
activation
tropomyosin
receptor
kinase
B
(TrkB),
expressed
both
peripheral
central
system.
has
been
implicated
several
neuropsychiatric
conditions
such
as
schizophrenia
anxio-depressive
disorders,
well
pain
states.
This
review
summarizes
evidence
for
critical
throughout
describes
contrasting
findings
its
pro-
anti-nociceptive
effects.
Different
cellular
sources
BDNF,
influence
on
neuroimmune
signaling
conditions,
different
cell
types
regions
described.
These
endogenous
levels,
downstream
mechanisms,
route
administration,
approaches
to
manipulate
could
explain
bidirectional
plasticity
modulation.
Finally,
current
knowledge
gaps
concerning
discussed,
including
sex-
pathway-specific
differences.
Molecules,
Год журнала:
2024,
Номер
29(15), С. 3560 - 3560
Опубликована: Июль 29, 2024
Tropomyosin
receptor
kinases
(Trks)
are
transmembrane
tyrosine
named
TrkA,
TrkB,
and
TrkC
encoded
by
the
NTRK1,
NTRK2,
NTRK3
genes,
respectively.
These
have
attracted
significant
attention
represent
a
promising
therapeutic
target
for
solid
tumor
treatment
due
to
their
vital
role
in
cellular
signaling
pathways.
First-generation
TRK
inhibitors,
i.e.,
Larotrectinib
sulfate
Entrectinib,
received
clinical
approval
2018
2019,
However,
use
of
these
inhibitors
was
significantly
limited
because
development
resistance
mutations.
Fortunately,
second-generation
Trk
inhibitor
Repotrectinib
(TPX-0005)
approved
FDA
November
2023,
while
Selitrectinib
(Loxo-195)
has
provided
an
effective
solution
this
issue.
Another
macrocycle-based
analog,
along
with
many
other
is
currently
trials.
Two
three
marketed
drugs
NTRK
fusion
cancers
feature
pyrazolo[1,5-
Frontiers in Molecular Neuroscience,
Год журнала:
2024,
Номер
17
Опубликована: Авг. 29, 2024
Brain
derived
neurotrophic
factor
(BDNF)
is
the
most
studied
trophic
in
central
nervous
system
(CNS),
and
its
role
maturation
of
neurons,
including
synapse
development
maintenance
has
been
investigated
intensely
for
over
three
decades.
The
primary
receptor
BDNF
tropomyosin
kinase
B
(TrkB),
which
broadly
expressed
as
two
isoforms
brain;
full
length
TrkB
(TrkB.FL)
receptor,
mainly
neurons
truncated
(TrkB.T1)
receptor.
We
recently
demonstrated
that
TrkB.T1
predominately
astrocytes,
appears
critical
astrocyte
morphological
maturation.
Given
BDNF/TrkB
pathway
healthy
brain
mature
CNS
function,
we
aimed
to
identify
molecular
underpinnings
cell-type
specific
expression
each
isoform.
Using
Nanopore
sequencing
enables
direct,
long
read
native
DNA,
profiled
DNA
methylation
patterns
entire
gene,
Ntrk2
,
both
astrocytes.
Here,
identified
robust
differences
isoform
associated
with
significantly
different
gene
cell
type.
Notably,
astrocytes
lower
5mC
methylation,
higher
5hmC
across
when
compared
differentially
methylated
sites
(DMSs)
found
regions
flanking
unique
protein
coding
sequence
(CDS).
These
data
suggest
may
provide
instruction
types.
