Molecular Neurodegeneration,
Год журнала:
2023,
Номер
18(1)
Опубликована: Ноя. 8, 2023
Abstract
DNA
sensing
is
a
pivotal
component
of
the
innate
immune
system
that
responsible
for
detecting
mislocalized
and
triggering
downstream
inflammatory
pathways.
Among
sensors,
cyclic
GMP-AMP
synthase
(cGAS)
primary
player
in
cytosolic
DNA,
including
foreign
from
pathogens
self-DNA
released
during
cellular
damage,
culminating
type
I
interferon
(IFN-I)
response
through
stimulator
genes
(STING)
activation.
IFN-I
cytokines
are
essential
mediating
neuroinflammation,
which
widely
observed
CNS
injury,
neurodegeneration,
aging,
suggesting
an
upstream
role
cGAS
pathway.
In
this
review,
we
summarize
latest
developments
on
cGAS-STING
DNA-driven
various
neurological
diseases
conditions.
Our
review
covers
current
understanding
molecular
mechanisms
activation
highlights
signaling
cell
types
central
peripheral
nervous
systems,
such
as
resident
brain
cells,
neurons,
glial
cells.
We
then
discuss
different
neurodegenerative
conditions,
tauopathies,
Alzheimer’s
disease,
Parkinson’s
amyotrophic
lateral
sclerosis,
well
aging
senescence.
Finally,
lay
out
advancements
research
development
inhibitors
assess
prospects
targeting
STING
therapeutic
strategies
wide
spectrum
diseases.
Signal Transduction and Targeted Therapy,
Год журнала:
2022,
Номер
7(1)
Опубликована: Ноя. 7, 2022
Abstract
Aging
is
accompanied
by
the
decline
of
organismal
functions
and
a
series
prominent
hallmarks,
including
genetic
epigenetic
alterations.
These
aging-associated
changes
include
DNA
methylation,
histone
modification,
chromatin
remodeling,
non-coding
RNA
(ncRNA)
regulation,
all
which
participate
in
regulation
aging
process,
hence
contribute
to
aging-related
diseases.
Therefore,
understanding
mechanisms
will
provide
new
avenues
develop
strategies
delay
aging.
Indeed,
interventions
based
on
manipulating
have
led
alleviation
or
extension
lifespan
animal
models.
Small
molecule-based
therapies
reprogramming
that
enable
rejuvenation
been
developed
for
ameliorating
reversing
conditions.
In
addition,
adopting
health-promoting
activities,
such
as
caloric
restriction,
exercise,
calibrating
circadian
rhythm,
has
demonstrated
Furthermore,
various
clinical
trials
intervention
are
ongoing,
providing
more
evidence
safety
efficacy
these
therapies.
Here,
we
review
recent
work
outline
advances
age-associated
A
better
critical
roles
epigenetics
process
lead
prevention
human
therapy
Journal of Biological Chemistry,
Год журнала:
2020,
Номер
295(13), С. 4134 - 4170
Опубликована: Фев. 15, 2020
Expansions
of
simple
tandem
repeats
are
responsible
for
almost
50
human
diseases,
the
majority
which
severe,
degenerative,
and
not
currently
treatable
or
preventable.
In
this
review,
we
first
describe
molecular
mechanisms
repeat-induced
toxicity,
is
connecting
link
between
repeat
expansions
pathology.
We
then
survey
alternative
DNA
structures
that
formed
by
expandable
review
evidence
formation
these
at
core
instability.
Next,
consequences
presence
long
structure-forming
level:
somatic
intergenerational
instability,
fragility,
mutagenesis.
discuss
reasons
gender
bias
in
instability
tissue
specificity
also
known
pathways
replication,
transcription,
repair,
chromatin
state
interact
thereby
promote
possible
persistence
disease-causing
genome.
suggesting
a
payoff
advantages
having
abundant
simple-sequence
eukaryotic
genome
function
evolvability.
Finally,
two
unresolved
fundamental
questions:
(i)
why
does
behavior
differ
model
systems
pedigrees,
(ii)
can
use
current
knowledge
on
to
cure
expansion
diseases?
