Nature Communications,
Год журнала:
2021,
Номер
12(1)
Опубликована: Фев. 24, 2021
Abstract
High-throughput
single-cell
epigenomic
assays
can
resolve
cell
type
heterogeneity
in
complex
tissues,
however,
spatial
orientation
is
lost.
Here,
we
present
combinatorial
indexing
on
Microbiopsies
Assigned
to
Positions
for
the
Assay
Transposase
Accessible
Chromatin,
or
sciMAP-ATAC,
as
a
method
highly
scalable,
spatially
resolved,
profiling
of
chromatin
states.
sciMAP-ATAC
produces
data
equivalent
quality
non-spatial
sci-ATAC
and
retains
positional
information
each
within
214
micron
cubic
region,
with
up
hundreds
tracked
positions
single
experiment.
We
apply
assess
cortical
lamination
adult
mouse
primary
somatosensory
cortex
human
visual
cortex,
where
produce
trajectories
integrate
our
single-nucleus
RNA
other
accessibility
datasets.
Finally,
characterize
progressive
nature
cerebral
ischemic
infarction
brain
using
model
transient
middle
artery
occlusion.
Redox Biology,
Год журнала:
2018,
Номер
15, С. 490 - 503
Опубликована: Фев. 3, 2018
The
human
brain
consumes
20%
of
the
total
basal
oxygen
(O2)
budget
to
support
ATP
intensive
neuronal
activity.
Without
sufficient
O2
demands,
activity
fails,
such
that,
even
transient
ischemia
is
neurodegenerative.
While
essentiality
function
clear,
how
oxidative
stress
causes
neurodegeneration
ambiguous.
Ambiguity
exists
because
many
reasons
why
susceptible
remain
obscure.
Many
are
erroneously
understood
as
deleterious
result
adventitious
derived
free
radical
and
non-radical
species
generation.
To
understand
underpin
stress,
one
must
first
re-cast
in
a
positive
light
their
deliberate
generation
enables
achieve
critical
functions
(e.g.
synaptic
plasticity)
through
redox
signalling
(i.e.
functionality).
Using
radicals
derivatives
signal
sensitises
when
goes
awry
negative
advance
mechanistic
understanding,
we
rationalise
13
stress.
Key
include
inter
alia
unsaturated
lipid
enrichment,
mitochondria,
calcium,
glutamate,
modest
antioxidant
defence,
active
transition
metals
neurotransmitter
auto-oxidation.
We
review
RNA
oxidation
an
underappreciated
cause
complex
interplay
between
each
reason
dictates
susceptibility
dynamic
context
neural
identity
dependent
manner.
Our
discourse
sets
stage
for
investigators
interrogate
biochemical
basis
health
disease.
Current Neuropharmacology,
Год журнала:
2018,
Номер
16(9), С. 1396 - 1415
Опубликована: Март 7, 2018
As
a
result
of
ischemia
or
hemorrhage,
blood
supply
to
neurons
is
disrupted
which
subsequently
promotes
cascade
pathophysiological
responses
resulting
in
cell
loss.
Many
mechanisms
are
involved
solely
combination
this
disorder
including
excitotoxicity,
mitochondrial
death
pathways,
and
the
release
free
radicals,
protein
misfolding,
apoptosis,
necrosis,
autophagy
inflammation.
Besides
neuronal
loss,
damage
loss
astrocytes
as
well
injury
white
matter
contributes
also
cerebral
injury.
The
core
problem
stroke
cells
makes
recovery
difficult
even
not
possible
late
states.
Acute
treatment
options
that
can
be
applied
for
mainly
targeting
re-establishment
flow
hence,
their
use
limited
due
effective
time
window
thrombolytic
agents.
However,
if
acute
exceeded,
starts
activation
pathways.
This
review
will
explore
most
updated
cellular
leading
stroke.
Ischemic
hemorrhagic
subarachnoid
hemorrhage
debated
light
novel
molecular
discussed.
PLoS Biology,
Год журнала:
2018,
Номер
16(6), С. e2004880 - e2004880
Опубликована: Июнь 7, 2018
N6-methyladenosine
(m6A)
RNA
methylation
is
the
most
abundant
modification
on
mRNAs
and
plays
important
roles
in
various
biological
processes.
The
formation
of
m6A
catalyzed
by
a
methyltransferase
complex
including
methyltransferase-like
3
(METTL3)
as
key
factor.
However,
vivo
functions
METTL3
mammalian
development
remain
unclear.
Here,
we
show
that
specific
inactivation
Mettl3
mouse
nervous
system
causes
severe
developmental
defects
brain.
conditional
knockout
(cKO)
mice
manifest
cerebellar
hypoplasia
caused
drastically
enhanced
apoptosis
newborn
granule
cells
(CGCs)
external
granular
layer
(EGL).
depletion–induced
loss
extended
half-lives
aberrant
splicing
events,
consequently
leading
to
dysregulation
transcriptome-wide
gene
expression
premature
CGC
death.
Our
findings
reveal
critical
role
METTL3-mediated
regulating
cerebellum.
Current Opinion in Neurobiology,
Год журнала:
2018,
Номер
48, С. 193 - 200
Опубликована: Янв. 30, 2018
The
restrictive
element-1
silencing
transcription
factor)/NRSF
(neuron-restrictive
factor
(NRSF)
is
a
transcriptional
repressor
which
acts
via
epigenetic
remodeling
to
silence
target
genes.
Emerging
evidence
indicates
that
REST
master
regulator
of
neuron-specific
genes
not
only
in
neurogenesis
and
neuronal
differentiation,
but
also
differentiated
neurons
during
the
critical
period
postnatal
brain
development,
where
it
plays
role
fine-tuning
involved
synaptic
plasticity,
normal
aging,
promotes
neuroprotection
by
repressing
oxidative
stress
β-amyloid
toxicity.
This
review
focuses
on
recent
findings
dysregulation
REST-dependent
provide
central
mechanism
progressive
neurodegeneration
associated
with
neurologic
disorders
diseases
including
global
ischemia,
stroke,
epilepsy,
Alzheimer's
Huntington's
disease.
Journal of Clinical Investigation,
Год журнала:
2022,
Номер
132(10)
Опубликована: Май 15, 2022
Alzheimer's
disease
and
related
dementias
(ADRD)
are
among
the
top
contributors
to
disability
mortality
in
later
life.
As
with
many
chronic
conditions,
aging
is
single
most
influential
factor
development
of
ADRD.
Even
older
adults
who
remain
free
dementia
throughout
their
lives,
cognitive
decline
neurodegenerative
changes
appreciable
advancing
age,
suggesting
shared
pathophysiological
mechanisms.
In
this
Review,
we
provide
an
overview
cognition,
brain
morphology,
neuropathological
protein
accumulation
across
lifespan
humans,
complementary
mechanistic
evidence
from
animal
models.
Next,
highlight
selected
processes
that
differentially
regulated
disease,
including
aberrant
autophagy,
mitochondrial
dysfunction,
cellular
senescence,
epigenetic
changes,
cerebrovascular
inflammation,
lipid
dysregulation.
We
summarize
research
clinical
translational
studies
link
biological
underlying
ADRD
pathogenesis.
Targeting
fundamental
may
represent
a
yet
relatively
unexplored
avenue
attenuate
both
age-related
Collaboration
fields
geroscience
neuroscience,
coupled
new
models
more
closely
align
human
processes,
necessary
advance
novel
therapeutic
discovery
realm.
