International Journal of Molecular Sciences,
Год журнала:
2022,
Номер
23(9), С. 4653 - 4653
Опубликована: Апрель 22, 2022
The
damage
and
repair
of
DNA
is
a
continuous
process
required
to
maintain
genomic
integrity.
double-strand
breaks
(DSBs)
are
the
most
lethal
type
require
timely
by
dedicated
machinery.
DSB
uniquely
important
nondividing,
post-mitotic
cells
central
nervous
system
(CNS).
These
long-lived
must
rely
on
intact
genome
for
lifetime
while
maintaining
high
metabolic
activity.
When
these
mechanisms
fail,
loss
certain
neuronal
populations
upset
delicate
neural
networks
higher
cognition
disrupt
vital
motor
functions.
Mammalian
engage
with
several
different
strategies
recognize
chromosomal
DSBs
based
cellular
context
cell
cycle
phase,
including
homologous
recombination
(HR)/homology-directed
(HDR),
microhomology-mediated
end-joining
(MMEJ),
classic
non-homologous
(NHEJ).
In
addition
pathways,
growing
body
evidence
has
emphasized
importance
response
(DDR)
signaling,
involvement
heterogeneous
nuclear
ribonucleoprotein
(hnRNP)
family
proteins
in
DSBs,
many
which
linked
age-associated
neurological
disorders.
this
review,
we
describe
contemporary
research
characterizing
mechanistic
roles
non-canonical
repair,
as
well
their
contributions
etiopathogenesis
selected
common
diseases.
FEBS Journal,
Год журнала:
2021,
Номер
289(8), С. 2013 - 2024
Опубликована: Янв. 18, 2021
Neurodegenerative
diseases,
including
Alzheimer's
disease
(AD)
and
Parkinson's
(PD),
are
characterized
by
progressive
memory
loss
motor
impairment.
Aging
is
a
major
risk
factor
for
neurodegenerative
diseases.
diseases
aging
often
develop
in
an
irreversible
manner
cause
significant
socioeconomic
burden.
When
considering
their
pathogenesis,
many
studies
usually
focus
on
mitochondrial
dysfunction
DNA
damage.
More
recently,
neuroinflammation,
autophagy
dysregulation,
SIRT1
inactivation
were
shown
to
be
involved
the
pathogenesis
of
aging.
In
addition,
uncovered
role
poly
(ADP‐ribose)‐polymerase‐1
(PARP1)
PARP1
links
cluster
stress
signals,
those
originated
inflammation
dysregulation.
this
review,
we
summarized
recent
research
progresses
aging,
with
emphasis
relationship
among
PARP1,
mitochondria,
autophagy.
We
discussed
possibilities
treating
through
targeting
PARP1.
Translational Neurodegeneration,
Год журнала:
2023,
Номер
12(1)
Опубликована: Апрель 14, 2023
Abstract
Redox
homeostasis
refers
to
the
balance
between
production
of
reactive
oxygen
species
(ROS)
as
well
nitrogen
(RNS),
and
their
elimination
by
antioxidants.
It
is
linked
all
important
cellular
activities
oxidative
stress
a
result
imbalance
pro-oxidants
antioxidant
species.
Oxidative
perturbs
many
activities,
including
processes
that
maintain
integrity
DNA.
Nucleic
acids
are
highly
therefore
particularly
susceptible
damage.
The
DNA
damage
response
detects
repairs
these
lesions.
Efficient
repair
essential
for
maintaining
viability,
but
they
decline
considerably
during
aging.
deficiencies
in
increasingly
described
age-related
neurodegenerative
diseases,
such
Alzheimer’s
disease,
Parkinson’s
amyotrophic
lateral
sclerosis
Huntington’s
disease.
Furthermore,
has
long
been
associated
with
conditions.
Moreover,
both
redox
dysregulation
increase
significantly
aging,
which
biggest
risk
factor
diseases.
However,
links
dysfunction
damage,
joint
contributions
pathophysiology
conditions,
only
just
emerging.
This
review
will
discuss
associations
address
increasing
evidence
an
major
source
disorders.
Understanding
connections
may
facilitate
better
understanding
disease
mechanisms,
ultimately
lead
design
therapeutic
strategies
based
on
preventing
Cell Communication and Signaling,
Год журнала:
2024,
Номер
22(1)
Опубликована: Май 24, 2024
Abstract
Aging
is
a
complex
and
multifaceted
process
involving
variety
of
interrelated
molecular
mechanisms
cellular
systems.
Phenotypically,
the
biological
aging
accompanied
by
gradual
loss
function
systemic
deterioration
multiple
tissues,
resulting
in
susceptibility
to
aging-related
diseases.
Emerging
evidence
suggests
that
closely
associated
with
telomere
attrition,
DNA
damage,
mitochondrial
dysfunction,
nicotinamide
adenine
dinucleotide
levels,
impaired
macro-autophagy,
stem
cell
exhaustion,
inflammation,
protein
balance,
deregulated
nutrient
sensing,
altered
intercellular
communication,
dysbiosis.
These
age-related
changes
may
be
alleviated
intervention
strategies,
such
as
calorie
restriction,
improved
sleep
quality,
enhanced
physical
activity,
targeted
longevity
genes.
In
this
review,
we
summarise
key
historical
progress
exploration
important
causes
anti-aging
strategies
recent
decades,
which
provides
basis
for
further
understanding
reversibility
phenotypes,
application
prospect
synthetic
biotechnology
therapy
also
prospected.
Molecules,
Год журнала:
2019,
Номер
24(23), С. 4410 - 4410
Опубликована: Дек. 3, 2019
Alzheimer's
disease
(AD)
is
a
neurodegenerative
that
usually
accompanied
by
aging,
increasingly
being
the
most
common
cause
of
dementia
in
elderly.
This
disorder
characterized
accumulation
beta
amyloid
plaques
(Aβ)
resulting
from
impaired
precursor
protein
(APP)
metabolism,
together
with
formation
neurofibrillary
tangles
and
tau
hyperphosphorylation.
The
exacerbated
production
reactive
oxygen
species
(ROS)
triggers
process
called
oxidative
stress,
which
increases
neuronal
cell
abnormalities,
often
followed
apoptosis,
leading
to
cognitive
dysfunction
dementia.
In
this
context,
development
new
therapies
for
AD
treatment
necessary.
Antioxidants,
instance,
are
promising
prevention
because
they
capable
disrupting
radical
chain
reaction,
reducing
ROS.
These
have
also
proven
be
adjunctive
conventional
treatments
making
them
more
effective.
sense,
several
recently
published
works
focused
their
attention
on
stress
antioxidant
species.
Therefore,
review
seeks
show
relevant
findings
these
studies.
Acta Neuropathologica Communications,
Год журнала:
2023,
Номер
11(1)
Опубликована: Март 31, 2023
Alzheimer's
disease
(AD)
is
a
neurodegenerative
disorder
with
neuronal
and
synaptic
losses
due
to
the
accumulation
of
toxic
amyloid
β
(Αβ)
peptide
oligomers,
plaques,
tangles
containing
tau
(tubulin-associated
unit)
protein.
While
familial
AD
caused
by
specific
mutations,
sporadic
more
common
appears
result
from
complex
chronic
brain
neuroinflammation
mitochondriopathies,
inducing
free
radicals'
accumulation.
In
aged
brain,
mutations
in
DNA
several
unfolded
proteins
participate
amyloidosis
response
effect
on
myelin
sheath
axons,
leading
cognitive
deficits
dementia.
Αβ
peptides
are
most
frequent
form
oligomers.
Accumulations
misfolded
during
years
alters
different
metabolic
mechanisms,
induce
inflammatory
immune
responses
consequences
cells.
Myelin
composition
architecture
may
appear
be
an
early
target
for
activity
Aβ
others
hydrophobic
proteins.
this
work,
we
describe
possible
role
alterations
genesis
onset
symptomatology.
We
propose
that
some
pathophysiological
clinical
forms
arise
structural
disorders
processes
myelination/demyelination
regions
where
non-functional
important.
these
forms,
primacy
deleterious
would
matter
questioning
initiating
neuropathology
primarily
fact
dysmyelination.
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(7), С. 6313 - 6313
Опубликована: Март 28, 2023
Parkinson’s
disease
(PD)
is
the
second
most
common
neurodegenerative
around
world;
however,
its
pathogenesis
remains
unclear
so
far.
Recent
advances
have
shown
that
DNA
damage
and
repair
deficiency
play
an
important
role
in
pathophysiology
of
PD.
There
growing
evidence
suggesting
involved
propagation
cellular
PD,
leading
to
neuropathology
under
different
conditions.
Here,
we
reviewed
current
work
on
First,
outlined
causes
Second,
described
potential
pathways
by
which
mediates
neurotoxicity
PD
discussed
precise
mechanisms
drive
these
processes
damage.
In
addition,
looked
ahead
interventions
targeting
repair.
Finally,
based
status
research,
key
problems
need
be
addressed
future
research
were
proposed.
