Decoding the Nectin Interactome: Implications for Brain Development, Plasticity, and Neurological Disorders
ACS Chemical Neuroscience,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 2, 2025
The
nectin
family
of
cell
adhesion
molecules
(CAMs)
comprising
nectins
and
nectin-like
has
emerged
as
a
key
regulator
various
pivotal
neural
processes,
including
neuronal
development,
migration,
synapse
formation,
plasticity.
Nectins
engage
in
homophilic
heterophilic
interactions
to
mediate
cell-cell
adhesion,
contributing
the
establishment
maintenance
circuits.
Their
extracellular
domains
facilitate
trans-synaptic
interactions,
while
intracellular
participate
signaling
cascades
influencing
cytoskeletal
dynamics
synaptic
function.
exhibition
distinct
localization
patterns
neurons,
astrocytes,
blood-brain
barrier
underscores
their
diverse
roles
brain.
dysregulation
been
implicated
several
neurological
disorders,
such
neurodevelopmental
depression,
schizophrenia,
Alzheimer's
disease.
This
review
examines
structural
functional
characteristics
distribution
molecular
mechanisms
governing
connectivity
cognition.
It
further
discusses
experimental
studies
unraveling
nectin-mediated
pathophysiology
potential
therapeutic
interventions
targeting
nectin-related
pathways.
Collectively,
this
comprehensive
analysis
highlights
significance
brain
function,
paving
way
for
future
research
directions
clinical
implications.
Language: Английский
Gene discovery and pleiotropic architecture of Chronic Pain in a Genome-wide Association Study of >1.2 million Individuals
medRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 5, 2025
ABSTRACT
Chronic
pain
is
highly
prevalent
worldwide,
and
genome-wide
association
studies
(GWAS)
have
identified
a
growing
number
of
chronic
loci.
To
further
elucidate
its
genetic
architecture,
we
leveraged
data
from
1,235,695
European
ancestry
individuals
across
three
biobanks.
In
meta-analytic
GWAS,
343
independent
loci
for
pain,
92
which
were
new.
Sex-specific
meta-analyses
revealed
115
(12
new)
males
(N
=
583,066)
12
(two
females
241,266).
Multi-omics
gene
prioritization
analyses
highlighted
490
genes
associated
with
through
their
effects
on
brain-
blood-specific
regulation.
Loci
increased
risk
also
multiple
other
traits,
Mendelian
randomization
showing
that
was
causally
psychiatric
disorders,
substance
use
C-reactive
protein
levels.
variants
exhibited
pleiotropic
associations
cortical
area
brain
structures.
This
study
expands
our
knowledge
the
genetics
pathogenesis,
highlighting
importance
pleiotropy
disorders
elucidating
multi-omic
pathophysiology.
Language: Английский
Multivariate, Multi-omic Analysis in 799,429 Individuals Identifies 134 Loci Associated with Somatoform Traits
medRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: July 29, 2024
Abstract
Somatoform
traits,
which
manifest
as
persistent
physical
symptoms
without
a
clear
medical
cause,
are
prevalent
and
pose
challenges
to
clinical
practice.
Understanding
the
genetic
basis
of
these
disorders
could
improve
diagnostic
therapeutic
approaches.
With
publicly
available
summary
statistics,
we
conducted
multivariate
genome-wide
association
study
(GWAS)
multi-omic
analysis
four
somatoform
traits—fatigue,
irritable
bowel
syndrome,
pain
intensity,
health
satisfaction—in
799,429
individuals
genetically
similar
Europeans.
Using
genomic
structural
equation
modeling,
GWAS
identified
134
loci
significantly
associated
with
common
factor,
including
44
not
significant
in
input
8
novel
for
traits.
Gene-property
analyses
highlighted
an
enrichment
genes
involved
synaptic
transmission
enriched
gene
expression
12
brain
tissues.
Six
genes,
members
CD300
family,
had
putatively
causal
effects
mediated
by
protein
abundance.
There
was
substantial
polygenic
overlap
(76-83%)
between
externalizing,
internalizing,
general
psychopathology
factors.
scores
were
most
strongly
obesity,
Type
2
diabetes,
tobacco
use
disorder,
mood/anxiety
independent
biobanks.
Drug
repurposing
suggested
potential
targets,
MEK
inhibitors.
Mendelian
randomization
indicated
potentially
protective
gut
microbiota,
Ruminococcus
bromii
.
These
biological
insights
provide
promising
avenues
treatment
development.
Language: Английский
Exploring the genetic and socioeconomic interplay between ADHD and anxiety disorders using Mendelian randomization
Frontiers in Psychiatry,
Journal Year:
2024,
Volume and Issue:
15
Published: Aug. 6, 2024
ADHD
and
anxiety
disorders
often
co-occur,
sharing
symptoms
dysfunctions,
yet
the
underlying
mechanisms
remain
elusive.
Language: Английский
A Multivariate Genome-Wide Association Study Reveals Neural Correlates and Common Biological Mechanisms of Psychopathology Spectra
medRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: April 9, 2024
There
is
considerable
comorbidity
between
externalizing
(EXT)
and
internalizing
(INT)
psychopathology.
Understanding
the
shared
genetic
underpinnings
of
these
spectra
crucial
for
advancing
knowledge
their
biological
bases
potential
health
impacts,
informing
empirical
models
like
Research
Domain
Criteria
(RDoC)
Hierarchical
Taxonomy
Psychopathology
(HiTOP).
We
conducted
a
multivariate
genome-wide
association
study
(GWAS)
EXT
INT
psychopathology
by
applying
genomic
structural
equation
modeling
to
summary
statistics
from
16
traits
in
European-ancestry
individuals
(n
=
16,400
1,074,629).
Downstream
analyses
explored
associations
across
RDoC
units
analysis
(i.e.,
genes,
molecules,
cells,
circuits,
physiology,
behaviors).
The
GWAS
identified
409
lead
single
nucleotide
polymorphisms
(SNPs)
EXT,
85
INT,
256
EXT+INT
shared)
traits.
Bivariate
causal
mixture
estimated
that
nearly
all
variants
overlapped,
despite
correlation
0.37
(SE
0.02).
Drug
repurposing
therapeutic
targets,
including
perturbagens
affecting
dopamine
serotonin
pathways.
genes
had
enriched
expression
GABAergic,
cortical,
hippocampal
neurons,
while
were
more
narrowly
linked
GABAergic
neurons.
liability
was
associated
with
reduced
grey
matter
volumes
amygdala
subcallosal
cortex.
These
findings
reveal
both
overlap
distinct
molecular
neurobiological
pathways
underlying
By
integrating
insights
HiTOP
frameworks,
this
advances
our
understanding
mechanisms
driving
dimensions
Language: Английский