Proceedings of the National Academy of Sciences,
Год журнала:
2021,
Номер
118(37)
Опубликована: Сен. 8, 2021
Significance
Impaired
neuronal
bioenergetics
and
neuroinflammation
are
thought
to
play
key
roles
in
the
progression
of
Alzheimer's
disease
(AD),
but
their
interplay
is
not
clear.
AD
mouse
brains
showed
lower
nicotinamide
adenine
dinucleotide
(NAD
+
)
levels
alterations
inflammation.
Treatment
mice
with
NR
reduced
neuroinflammation,
attenuated
DNA
damage,
prevented
cellular
senescence.
We
present
evidence
that
beneficial
effects
riboside
(NR)
are,
part,
through
a
cyclic
GMP-AMP
synthase
(cGAS)–stimulator
interferon
genes
(STING)-dependent
pathway.
damage
was
increased
by
NR.
Both
cGAS–STING
NAD
pathways
potential
therapeutic
targets
for
AD.
Frontiers in Cell and Developmental Biology,
Год журнала:
2021,
Номер
9
Опубликована: Март 29, 2021
Cellular
senescence
is
a
stable
cell
cycle
arrest
that
can
be
triggered
in
normal
cells
response
to
various
intrinsic
and
extrinsic
stimuli,
as
well
developmental
signals.
Senescence
considered
highly
dynamic,
multi-step
process,
during
which
the
properties
of
senescent
continuously
evolve
diversify
context
dependent
manner.
It
associated
with
multiple
cellular
molecular
changes
distinct
phenotypic
alterations,
including
proliferation
unresponsive
mitogenic
stimuli.
Senescent
remain
viable,
have
alterations
metabolic
activity
undergo
dramatic
gene
expression
develop
complex
senescence-associated
secretory
phenotype.
compromise
tissue
repair
regeneration,
thereby
contributing
toward
aging.
Removal
attenuate
age-related
dysfunction
extend
health
span.
also
act
potent
anti-tumor
mechanism,
by
preventing
potentially
cancerous
cells.
program
acts
double-edged
sword,
both
beneficial
detrimental
effects
on
organism,
an
example
evolutionary
antagonistic
pleiotropy.
Activation
p53/p21
WAF1/CIP1
p16
INK4A
/pRB
tumor
suppressor
pathways
play
central
role
regulating
senescence.
Several
other
recently
been
implicated
mediating
Herein
we
review
mechanisms
underlie
growth
particular
focus
why
stop
dividing,
stability
arrest,
hypersecretory
phenotype
how
different
are
all
integrated.
Signal Transduction and Targeted Therapy,
Год журнала:
2020,
Номер
5(1)
Опубликована: Апрель 30, 2020
Abstract
Radiotherapy
is
one
of
the
most
common
countermeasures
for
treating
a
wide
range
tumors.
However,
radioresistance
cancer
cells
still
major
limitation
radiotherapy
applications.
Efforts
are
continuously
ongoing
to
explore
sensitizing
targets
and
develop
radiosensitizers
improving
outcomes
radiotherapy.
DNA
double-strand
breaks
lethal
lesions
induced
by
ionizing
radiation
can
trigger
series
cellular
damage
responses
(DDRs),
including
those
helping
recover
from
injuries,
such
as
activation
sensing
early
transduction
pathways,
cell
cycle
arrest,
repair.
Obviously,
these
protective
DDRs
confer
tumor
radioresistance.
Targeting
DDR
signaling
pathways
has
become
an
attractive
strategy
overcoming
radioresistance,
some
important
advances
breakthroughs
have
already
been
achieved
in
recent
years.
On
basis
comprehensively
reviewing
signal
we
provide
update
on
novel
promising
druggable
emerging
that
be
exploited
radiosensitization.
We
further
discuss
identified
preclinical
studies,
current
clinical
trials,
application
chemical
inhibitors
targeting
key
proteins,
DNA-PKcs
(DNA-dependent
protein
kinase,
catalytic
subunit),
ATM/ATR
(ataxia–telangiectasia
mutated
Rad3-related),
MRN
(MRE11-RAD50-NBS1)
complex,
PARP
(poly[ADP-ribose]
polymerase)
family,
MDC1,
Wee1,
LIG4
(ligase
IV),
CDK1,
BRCA1
(BRCA1
C
terminal),
CHK1,
HIF-1
(hypoxia-inducible
factor-1).
Challenges
radiation-induced
targeted
therapy
also
discussed
based
achievements
biological
field
