D-Aspartate
and
D-Serine
serve
as
primary
agonists
at
glutamate
receptors,
playing
a
crucial
role
in
modulating
synaptic
plasticity
cell
migration
within
the
central
nervous
system.
The
pre-cise
regulation
of
their
levels
is
essential
intricately
linked
to
expression
synthetic
catabolic
enzymes,
which
are,
turn,
primarily
influenced
by
epigenetic
modifications.
In
comprehensive
analysis,
we
examined
methylation
profiles
promoters
transcription
start
sites
critical
genes
associated
with
metabolism
human
post-mortem
brain
tissues
sourced
from
normal
individuals
those
diagnosed
schizo-phrenia.
Our
approach
involved
qualitative
method
capable
identifying
specific
families
methylated
alleles
known
epialleles,
sharing
common
pattern
non-contiguous
CpGs,
referred
cores.
These
traits
exhibit
stability
consistency
com-plex
populations
diverse
DNA-methylated
molecules.
findings
reveal
area-specific
signatures
DDO,
DAO
DAOA
serving
distinctive
markers
that
differentiate
areas
affected
schizophrenia.
patterns
align
reported
high
low
observed
schizophrenic
areas.
study
suggests
potential
link
between
modifications
dysreg-ulation
these
neurotransmitters
European Archives of Psychiatry and Clinical Neuroscience,
Journal Year:
2023,
Volume and Issue:
273(7), P. 1557 - 1566
Published: March 27, 2023
Abstract
Schizophrenia
is
a
psychiatric
disorder
characterised
by
symptoms
in
three
domains:
positive
(e.g.
delusions,
hallucinations),
negative
social
withdrawal,
lack
of
motivation)
and
cognitive
working
memory
executive
function
impairment).
Cognitive
impairment
associated
with
schizophrenia
(CIAS)
major
burden
for
patients
negatively
impacts
many
aspects
patient’s
life.
Antipsychotics
are
the
standard-of-care
treatment
but
only
address
symptoms.
So
far
there
no
approved
pharmacotherapies
CIAS.
Iclepertin
(BI
425809)
novel,
potent
selective
glycine
transporter
1
(GlyT1)
inhibitor,
under
development
Boehringer
Ingelheim
Phase
I
studies
have
shown
it
to
be
safe
well
tolerated
healthy
volunteers,
central
target
engagement
(inhibition
GlyT1)
was
achieved
dose-dependent
manner
from
5
50
mg
volunteers.
A
II
study
has
demonstrated
that
iclepertin
improves
cognition
at
doses
10
25
mg.
III
ongoing
confirm
these
initial
safety
efficacy
findings
dose,
if
successful,
could
become
first
pharmacotherapy
used
treat
Schizophrenia Bulletin Open,
Journal Year:
2024,
Volume and Issue:
5(1)
Published: Jan. 1, 2024
Abstract
Cognitive
Impairment
Associated
with
Schizophrenia
(CIAS)
represents
one
of
the
core
dimensions
Spectrum
Disorders
(SSD),
an
important
negative
impact
on
real-world
functional
outcomes
people
living
SSD.
Treatment
CIAS
a
therapeutic
goal
considerable
importance,
and
while
cognition-oriented
evidence-based
psychosocial
interventions
are
available,
effective
pharmacological
treatment
could
represent
game-changer
in
lives
The
present
critical
review
reports
discusses
evidence
regarding
effects
several
agents
that
available
clinical
practice
or
under
study,
commenting
both
current
future
perspectives
treatment.
In
particular,
antipsychotic
medications,
anticholinergic
benzodiazepines,
which
currently
commonly
used
SSD,
iclepertin,
d-serine,
luvadaxistat,
xanomeline-trospium,
ulotaront,
anti-inflammatory
molecules,
oxytocin,
undergoing
regulatory
trials
can
be
considered
as
experimental
agents,
will
reported
discussed.
Currently,
do
not
appear
to
provide
substantial
benefits
CIAS,
but
accurate
management
medications
avoiding
treatments
further
exacerbate
strategies.
Some
molecules
being
investigated
Phase
2
3
have
provided
very
promising
preliminary
results,
more
information
is
required
assess
their
effectiveness
contexts
clear
recommendations
use
practice.
results
ongoing
studies
reveal
whether
any
these
awaited
CIAS.
ACS Omega,
Journal Year:
2024,
Volume and Issue:
9(5), P. 5084 - 5099
Published: Jan. 26, 2024
The
absolute
configuration
dictates
the
biological
role
of
chiral
molecules
in
living
world.
This
is
best
exemplified
by
all
ribosomally
synthesized
polypeptides
having
amino
acids
only
l-configuration.
However,
d-amino
are
also
associated
with
various
vital
processes
such
as
peptidoglycan
bacterial
cell
wall,
ligands
for
neurotransmitters,
involved
signaling,
and
precursors
metabolites,
to
name
a
few.
occurrence
both
l-
d-enantiomers
systems
necessitates
presence
enzymes
that
exhibit
stereoselectivity
recognition
substrates.
mini-review
summarizes
overall
mechanistic
insights
into
interconversion
acid
racemases.
We
discuss
structural,
mechanistic,
evolutionary
relationship
four
crucial
catalyze
oxidative
deamination
or
their
physiological
microbes
higher
organisms.
highlight
implications
oxidase
d-aspartate
human
health
diseases
applications
drug
targets.
Finally,
we
summarize
potential
microbially
obtained
chiral-selective
biocatalysts
industrial
purposes.
Biomedicines,
Journal Year:
2024,
Volume and Issue:
12(7), P. 1518 - 1518
Published: July 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.
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(22), P. 12410 - 12410
Published: Nov. 19, 2024
In
neuroscience
research,
chiral
metabolomics
is
an
emerging
field,
in
which
D-amino
acids
play
important
role
as
potential
biomarkers
for
neurological
diseases.
The
targeted
analysis
of
the
brain
metabolome,
employing
liquid
chromatography
(LC)
coupled
to
mass
spectrometry
(MS),
a
pivotal
approach
identification
This
review
provides
overview
diseases
and
state-of-the-art
strategies
enantioselective
amino
(AAs)
biological
samples
investigate
their
putative
Fluctuations
(D-AAs)
levels
can
be
related
pathology
diseases,
example,
through
modulation
N-methyl-D-aspartate
receptors
neurotransmission.
Because
trace
presence
these
biomolecules
mammals
complex
nature
matrices,
highly
sensitive
selective
analytical
methods
are
essential.
Derivatization
with
reagents
highlighted
critical
tools
enhancing
detection
capabilities.
latest
advances
derivatization
reactions,
LC-MS/MS
analysis,
have
improved
quantification
AAs
allow
separation
several
metabolites
single
run.
enhanced
performances
provide
accurate
correlation
between
specific
D-AA
profiles
disease
states,
allowing
better
understanding
drug
effects
on
brain.
Nutrients,
Journal Year:
2023,
Volume and Issue:
15(13), P. 2892 - 2892
Published: June 26, 2023
Recent
scientific
research
suggests
that
amino
acids
(AA)
are
not
only
the
"building
bricks"
of
protein
synthesis
but
may
also
be
considered
"metabokines"
[...].
D-Aspartate
and
D-Serine
serve
as
primary
agonists
at
glutamate
receptors,
playing
a
crucial
role
in
modulating
synaptic
plasticity
cell
migration
within
the
central
nervous
system.
The
pre-cise
regulation
of
their
levels
is
essential
intricately
linked
to
expression
synthetic
catabolic
enzymes,
which
are,
turn,
primarily
influenced
by
epigenetic
modifications.
In
comprehensive
analysis,
we
examined
methylation
profiles
promoters
transcription
start
sites
critical
genes
associated
with
metabolism
human
post-mortem
brain
tissues
sourced
from
normal
individuals
those
diagnosed
schizo-phrenia.
Our
approach
involved
qualitative
method
capable
identifying
specific
families
methylated
alleles
known
epialleles,
sharing
common
pattern
non-contiguous
CpGs,
referred
cores.
These
traits
exhibit
stability
consistency
com-plex
populations
diverse
DNA-methylated
molecules.
findings
reveal
area-specific
signatures
DDO,
DAO
DAOA
serving
distinctive
markers
that
differentiate
areas
affected
schizophrenia.
patterns
align
reported
high
low
observed
schizophrenic
areas.
study
suggests
potential
link
between
modifications
dysreg-ulation
these
neurotransmitters
BMC Psychiatry,
Journal Year:
2024,
Volume and Issue:
24(1)
Published: April 19, 2024
Despite
ongoing
research,
the
underlying
causes
of
schizophrenia
remain
unclear.
Aspartate
and
asparagine,
essential
amino
acids,
have
been
linked
to
in
recent
studies,
but
their
causal
relationship
is
still
This
study
used
a
bidirectional
two-sample
Mendelian
randomization
(MR)
method
explore
between
aspartate
asparagine
with
schizophrenia.
