There
are
no
therapies
approved
for
the
core
traits
of
autism,
nor
most
genetic
syndromes
linked
to
condition.But
there
many
under
investigation,
and
those
that
do
come
fruition
will
likely
target
one
three
levels
human
biology,
according
an
expert
review
published
in
February
Translational
Psychiatry:
DNA,
mRNA
or
proteins.Such
treatments
could
take
form
gene
therapies,
antisense
oligonucleotides
(ASOs)
smallmolecule
drugs,
respectively,
lead
investigator
Lilia
Iakoucheva,
professor
psychiatry
at
University
California,
San
Diego,
Derek
Hong,
who
worked
on
paper
as
a
graduate
student
Iakoucheva's
lab.Spectrum
caught
up
with
Iakoucheva
Hong
discuss
their
ideas.
This
interview
has
been
edited
length
clarity.Spectrum:
In
paper,
you
say
it's
time
shift
away
from
identifying
more
autism-linked
mutations
doing
something
about
treating
them.Could
talk
little
bit
that?Lilia
Iakoucheva:
What
I
mean
is
we
should
probably
advance
both
fronts.Autism
rare
variants
associated
it,
which
means
have
lots
low-hanging
fruit,
right?I
did
not
stop
identification,
but
think
also
therapies.Whole-genome
sequencing
help
identify
interplay
between
de
novo
common
inherited
alleles.There
evidence
now
play
very
important
role
genetics
especially
cannot
find
high-confidence
variant.Derek
Hong:
To
add
that,
feel
like
recent
whole-exome
results
drove
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 5, 2025
Advances
in
single-cell
sequencing
and
CRISPR
technologies
have
enabled
detailed
case-control
comparisons
experimental
perturbations
at
resolution.
However,
uncovering
causal
relationships
observational
genomic
data
remains
challenging
due
to
selection
bias
inadequate
adjustment
for
unmeasured
confounders,
particularly
heterogeneous
datasets.
To
address
these
challenges,
we
introduce
causarray,
a
doubly
robust
inference
framework
analyzing
array-based
both
bulk-cell
levels.
causarray
integrates
generalized
confounder
method
account
confounders
employs
semiparametric
with
flexible
machine
learning
techniques
ensure
statistical
estimation
of
treatment
effects.
Benchmarking
results
show
that
robustly
separates
effects
from
while
preserving
biological
signals
across
diverse
settings.
We
also
apply
two
studies:
(1)
an
vivo
Perturb-seq
study
autism
risk
genes
developing
mouse
brains
(2)
casecontrol
Alzheimer’s
disease
using
three
human
brain
transcriptomic
In
applications,
identifies
clustered
multiple
consistent
causally
affected
datasets,
biologically
relevant
pathways
directly
linked
neuronal
development
synaptic
functions
are
critical
understanding
pathology.
Journal of Molecular Biology,
Год журнала:
2023,
Номер
435(24), С. 168354 - 168354
Опубликована: Ноя. 5, 2023
Mutations
causing
loss
of
PTEN
lipid
phosphatase
activity
can
promote
cancer,
benign
tumors
(PHTS),
and
neurodevelopmental
disorders
(NDDs).
Exactly
how
they
preferentially
trigger
distinct
phenotypic
outcomes
has
been
puzzling.
Here,
we
demonstrate
that
mutations
differentially
allosterically
bias
P
loop
dynamics
its
connection
to
the
catalytic
site,
affecting
activity.
NDD-related
are
likely
sample
conformations
functional
wild-type
state,
while
sampled
for
strong,
cancer-related
driver
mutation
hotspots
favor
catalysis-primed
conformations,
suggesting
NDD
be
weaker,
our
large-scale
simulations
show
why.
Prenatal
isoform
expression
data
suggest
exons
5
7,
which
harbor
mutations,
as
cancer-risk
carriers.
Since
cancer
requires
more
than
a
single
mutation,
conformational
genomic
analysis
helps
discover
same
protein
foster
different
clinical
manifestations,
articulates
role
co-occurring
background
latent
uncovers
relationships
splicing
life
expectancy.
Journal of Neurodevelopmental Disorders,
Год журнала:
2024,
Номер
16(1)
Опубликована: Июль 5, 2024
Abstract
Background
A
sizeable
proportion
of
pathogenic
genetic
variants
identified
in
young
children
tested
for
congenital
differences
are
associated
with
neurodevelopmental
psychiatric
disorders
(NPD).
In
this
growing
group,
a
diagnosis
often
precedes
the
emergence
diagnosable
developmental
concerns.
Here,
we
describe
DAGSY
(Developmental
Assessment
Genetically
Susceptible
Youth),
novel
interdisciplinary
‘genetic-diagnosis-first’
clinic
integrating
psychiatric,
psychological
and
expertise,
report
our
first
observations
feedback
from
families
referring
clinicians.
Methods
We
retrieved
data
on
referral
sources
indications,
NPD
diagnoses
recommendations
seen
at
between
2018
2022.
Through
survey,
obtained
twenty
eleven
Results
159
(mean
age
10.2
years,
57.2%
males)
completed
an
(psychiatry,
psychology,
counselling)
assessment
during
period.
Of
these,
69.8%
had
microdeletion
or
microduplication,
21.5%
sequence-level
variant,
4.4%
chromosomal
disorder,
variant
unknown
significance
emerging
evidence
pathogenicity.
One
four
did
not
have
prior
diagnosis,
to
was
motivated
by
their
vulnerability
alone.
Following
assessment,
76.7%
received
least
one
new
most
frequently
intellectual
disability
(24.5%),
anxiety
(20.7%),
autism
spectrum
(18.9%)
specific
learning
(16.4%)
disorder.
Both
clinicians
responding
survey
expressed
satisfaction,
but
also
highlighted
some
areas
potential
improvement.
Conclusions
addresses
unmet
clinical
need
that
confer
increased
provides
crucial
platform
research
area.
can
serve
as
model
clinics
child
psychiatry,
psychology
genetics,
addressing
both
needs
population.
Molecular and Cellular Biochemistry,
Год журнала:
2023,
Номер
479(5), С. 1199 - 1221
Опубликована: Июнь 26, 2023
Abstract
Prickle
is
an
evolutionarily
conserved
family
of
proteins
exclusively
associated
with
planar
cell
polarity
(PCP)
signalling.
This
signalling
pathway
provides
directional
and
positional
cues
to
eukaryotic
cells
along
the
plane
epithelial
sheet,
orthogonal
both
apicobasal
left–right
axes.
Through
studies
in
fruit
fly
Drosophila
,
we
have
learned
that
PCP
manifested
by
spatial
segregation
two
protein
complexes,
namely
Prickle/Vangl
Frizzled/Dishevelled.
While
Vangl,
Frizzled,
Dishevelled
been
extensively
studied,
has
largely
neglected.
likely
because
its
role
vertebrate
development
pathologies
still
being
explored
not
yet
fully
understood.
The
current
review
aims
address
this
gap
summarizing
our
knowledge
on
cover
their
broad
versatility.
Accumulating
evidence
suggests
involved
many
developmental
events,
contributes
homeostasis,
can
cause
diseases
when
expression
properties
are
deregulated.
highlights
importance
development,
discusses
implications
Prickle-dependent
pathology,
points
out
blind
spots
or
potential
links
regarding
Prickle,
which
could
be
studied
further.
Macromolecular Bioscience,
Год журнала:
2024,
Номер
24(6)
Опубликована: Янв. 24, 2024
Hydrogels
are
3D
networks
swollen
with
water.
They
biocompatible,
strong,
and
moldable
emerging
as
a
promising
biomedical
material
for
regenerative
medicine
tissue
engineering
to
deliver
therapeutic
genes.
The
excellent
natural
extracellular
matrix
simulation
properties
of
hydrogels
enable
them
be
co-cultured
cells
or
enhance
the
expression
viral
non-viral
vectors.
Its
biocompatibility,
high
strength,
degradation
performance
also
make
action
process
carriers
in
tissues
more
ideal,
making
it
an
ideal
material.
It
has
been
shown
that
hydrogel-based
gene
delivery
technologies
have
potential
play
therapy-relevant
roles
organs
such
bone,
cartilage,
nerve,
skin,
reproductive
organs,
liver
animal
experiments
preclinical
trials.
This
paper
reviews
recent
articles
on
explains
manufacture,
applications,
developmental
timeline,
limitations,
future
directions
techniques.
Biomolecules,
Год журнала:
2023,
Номер
13(9), С. 1301 - 1301
Опубликована: Авг. 24, 2023
Neuroplasticity
is
a
crucial
property
of
the
central
nervous
system
to
change
its
activity
in
response
intrinsic
or
extrinsic
stimuli.
This
mainly
achieved
through
promotion
changes
epigenome.
One
epi-drivers
priming
this
process
suberoylanilide
hydroxamic
acid
(SAHA
Vorinostat),
pan-histone
deacetylase
inhibitor
that
modulates
and
promotes
neuroplasticity
healthy
disease
conditions.
Knowledge
specific
molecular
induced
by
epidrug
an
important
area
neuro-epigenetics
for
identification
new
compounds
treat
cognition
impairment
and/or
epilepsy.
In
review,
we
summarize
findings
obtained
cellular
animal
models
various
brain
disorders,
highlighting
multiple
mechanisms
activated
SAHA,
such
as
improvement
memory,
learning
behavior,
correction
faulty
neuronal
functioning.
Supporting
evidence,
vitro
vivo
data
underline
how
SAHA
positively
regulates
expression
genes
microtubule
dynamics,
induces
neurite
outgrowth
spine
density,
enhances
synaptic
transmission
potentiation.
particular,
outline
studies
regarding
neurodevelopmental
disorders
with
pharmaco-resistant
seizures
severe
cognitive
date
lack
effective
drug
treatments
which
could
ameliorate
defective
neuroplasticity.
