Current Opinion in Neurobiology,
Год журнала:
2024,
Номер
90, С. 102962 - 102962
Опубликована: Дек. 27, 2024
Autism
spectrum
disorders
(ASD)
are
substantially
heterogeneous
neuropsychiatric
conditions
with
over
a
thousand
associated
genetic
factors
and
various
environmental
influences,
such
as
infection
nutrition.
Additionally,
males
four
times
more
likely
than
females
to
be
affected.
This
heterogeneity
underscores
the
need
uncover
common
molecular
features
within
ASD.
Recent
studies
have
revealed
interactions
among
predispositions,
factors,
sex
that
may
critical
ASD
etiology.
review
focuses
on
emerging
evidence
for
impact
of
nutrients-particularly
zinc
amino
acids-on
ASD,
demonstrated
in
mouse
models
human
studies.
These
nutrients
been
shown
influence
synaptic
signaling,
dendritic
spine
formation,
behaviors
linked
autism.
Furthermore,
sex-based
differences
nutritional
requirements,
especially
acids,
contribute
observed
male
bias
autism,
indicating
between
could
integral
understanding
potentially
mitigating
symptoms.
Pharmaceuticals,
Год журнала:
2024,
Номер
17(5), С. 639 - 639
Опубликована: Май 15, 2024
Neurodegenerative
disorders
(NDs)
include
a
range
of
chronic
conditions
characterized
by
progressive
neuronal
loss,
leading
to
cognitive,
motor,
and
behavioral
impairments.
Common
examples
Alzheimer's
disease
(AD)
Parkinson's
(PD).
The
global
prevalence
NDs
is
on
the
rise,
imposing
significant
economic
social
burdens.
Despite
extensive
research,
mechanisms
underlying
remain
incompletely
understood,
hampering
development
effective
treatments.
Excitotoxicity,
particularly
glutamate-mediated
excitotoxicity,
key
pathological
process
implicated
in
NDs.
Targeting
N-methyl-D-aspartate
(NMDA)
receptor,
which
plays
central
role
holds
therapeutic
promise.
However,
challenges,
such
as
blood-brain
barrier
penetration
adverse
effects,
extrapyramidal
have
hindered
success
many
NMDA
receptor
antagonists
clinical
trials.
This
review
explores
molecular
antagonists,
emphasizing
their
structure,
function,
types,
future
prospects
treating
research
competitive
noncompetitive
quest
for
treatments
still
faces
hurdles.
partly
because
same
that
necessitates
blockage
under
also
responsible
normal
physiological
function
receptors.
Allosteric
modulation
receptors
presents
potential
alternative,
with
GluN2B
subunit
emerging
attractive
target
due
its
enrichment
presynaptic
extrasynaptic
receptors,
are
major
contributors
excitotoxic-induced
cell
death.
low
side-effect
profiles,
selective
like
ifenprodil
radiprodil
encountered
obstacles
poor
bioavailability
Moreover,
selectivity
these
often
relative,
they
been
shown
bind
other
GluN2
subunits,
albeit
minimally.
Recent
advancements
developing
phenanthroic
naphthoic
acid
derivatives
offer
promise
enhanced
GluN2B,
GluN2A
or
GluN2C/GluN2D
improved
pharmacodynamic
properties.
Additional
challenges
antagonist
conflicting
preclinical
results,
well
complexity
neurodegenerative
poorly
defined
subtypes.
Although
multifunctional
agents
targeting
multiple
degenerative
processes
being
explored,
data
limited.
Designing
antagonists/modulators
polycyclic
moieties
multitarget
properties
would
be
addressing
disorders.
understanding
structure
coupled
collaborative
efforts
drug
design,
imperative
realizing
antagonists/modulators.
Brain Sciences,
Год журнала:
2025,
Номер
15(2), С. 169 - 169
Опубликована: Фев. 9, 2025
Cerebral
lateralisation
is
a
core
organising
principle
of
the
brain
that
characterised
by
complex
pattern
hemispheric
specialisations
and
interhemispheric
interactions.
In
various
mental
disorders,
functional
and/or
structural
asymmetries
are
changed
compared
to
healthy
controls,
these
alterations
may
contribute
primary
symptoms
cognitive
impairments
specific
disorder.
Since
multiple
genetic
epigenetic
factors
influence
both
pathogenesis
illness
development
asymmetries,
it
likely
neural
developmental
pathways
overlap
or
even
causally
intertwined,
although
timing,
magnitude,
direction
interactions
vary
depending
on
However,
underlying
steps
neuronal
mechanisms
still
unclear.
this
review
article,
we
briefly
summarise
what
know
about
structural,
functional,
relationships
outline
hypothetical
connections,
which
could
be
investigated
in
appropriate
animal
models.
Altered
cerebral
features
disorder,
as
trigger
neuropathogenesis
embedded
asymmetrical
organisation
developing
brain.
Therefore,
occurrence
severity
processing
cognition
probably
cannot
understood
independently
lateralised
intra-
networks.
Conversely,
impaired
cellular
processes
can
also
hinder
favourable
asymmetry
lead
deficits
particular.
Physiological Research,
Год журнала:
2024,
Номер
Suppl 1, С. S413 - S434
Опубликована: Авг. 22, 2024
N-methyl-D-aspartate
receptors
(NMDARs)
are
a
subtype
of
ionotropic
glutamate
critical
for
synaptic
transmission
and
plasticity,
the
development
neural
circuits.
Rare
or
de-novo
variants
in
GRIN
genes
encoding
NMDAR
subunits
have
been
associated
with
neurodevelopmental
disorders
characterized
by
intellectual
disability,
developmental
delay,
autism,
schizophrenia,
epilepsy.
In
recent
years,
some
disease-associated
using
recombinant
expressed
non-neuronal
cells,
few
also
studied
neuronal
preparations
animal
models.
Here
we
review
current
literature
on
functional
evaluation
human
GRIN1,
GRIN2A
GRIN2B
at
all
levels
analysis.
Focusing
impact
different
patient
level
receptor
function,
discuss
effects
agonist
co-agonist
affinity,
channel
open
probability,
cell
surface
expression.
We
consider
how
such
receptor-level
information
may
be
used
to
classify
as
gain-of-function
loss-of-function,
limitations
this
classification
synaptic,
cellular,
system
level.
Together
work
many
laboratories
worldwide
yields
valuable
insights
into
structure
represents
significant
progress
effort
understand
treat
disorders.
Keywords:
NMDA
,
genes,
Genetic
variants,
Electrophysiology,
Synapse,
Animal
Biomedicines,
Год журнала:
2024,
Номер
12(7), С. 1518 - 1518
Опубликована: Июль 8, 2024
Glycine
plays
a
pivotal
role
in
the
Central
Nervous
System
(CNS),
being
major
inhibitory
neurotransmitter
as
well
co-agonist
of
Glutamate
at
excitatory
NMDA
receptors.
Interactions
involving
and
other
neurotransmitters
are
subject
different
studies.
Functional
interactions
among
include
modulation
release
through
release-regulating
receptors
but
also
transporter-mediated
mechanisms.
Many
involve
amino
acid
transmitters
Glycine,
Glutamate,
GABA.
Different
studies
published
during
last
two
decades
investigated
number
depth
nerve
terminal
level
CNS
areas,
providing
details
mechanisms
involved
suggesting
pathophysiological
significances.
Here,
this
evidence
is
reviewed
considering
additional
recent
information
available
literature,
with
special
(but
not
exclusive)
focus
on
glycinergic
neurotransmission
Glycine–Glutamate
interactions.
Some
possible
pharmacological
implications,
although
partly
speculative,
discussed.
Dysregulations
glutamatergic
transmission
relevant
pathologies.
Pharmacological
interventions
targets
(including
transporters)
under
study
to
develop
novel
therapies
against
serious
pathological
states
including
pain,
schizophrenia,
epilepsy,
neurodegenerative
diseases.
Although
limitations,
it
hoped
possibly
contribute
better
understanding
complex
between
glycine-mediated
transmitters,
view
current
interest
potential
drugs
acting
“glycinergic”
targets.
Some
of
neurodegenerative
diseases
may
be
characterized
by
continuing
behavioral
and
cognitive
dysfunction
that
contains
memory
loss
and/or
apathy.
Alzheimer's
disease
is
the
most
typical
type
such
deficit
cognition
alteration
behavior.
Despite
huge
efforts
against
disease,
there
has
been
yet
no
successful
treatment
for
this
disease.
Interestingly,
several
possible
risk
genes
to
are
frequently
expressed
within
brain
cells,
which
also
linked
cholesterol
metabolism,
lipid
transport,
exosomes
caveolae
formation,
suggesting
a
therapeutic
target
consider
dysfunctions.
modulation
autophagy/mitophagy
with
glucagon-like
peptide-1
(GLP-1)
N-methyl-d-aspartate
(NMDA)
receptors
signaling
offer
novel
approach
prevent
alleviate
dysfunction.
A
paradigm
both
GLP-1
NMDA
at
sites
promising
crucial
dysfunctions
presented
here,
might
able
modify
progression
This
research
direction
open
potential
move
clinical
care
toward
disease-modifying
strategies
maximal
benefits
patients
without
detrimental
adverse
events
diseases.
