Life,
Год журнала:
2023,
Номер
13(4), С. 970 - 970
Опубликована: Апрель 8, 2023
Alzheimer’s
disease
(AD),
a
progressive
and
chronic
neurodegenerative
syndrome,
is
categorized
by
cognitive
memory
damage
caused
the
aggregations
of
abnormal
proteins,
specifically
including
Tau
proteins
β-amyloid
in
brain
tissue.
Moreover,
mitochondrial
dysfunctions
are
principal
causes
AD,
which
associated
with
mitophagy
impairment.
Investigations
exploring
pharmacological
therapies
alongside
AD
have
explicitly
concentrated
on
molecules
accomplished
preventing/abolishing
gatherings
abovementioned
mitochondria
damages.
Mitophagy
removal
dead
autophagy
process.
Damages
mitophagy,
manner
diversified
degeneracy
resulting
an
ongoing
aggregation
malfunctioning
mitochondria,
were
also
suggested
to
support
AD.
Recently,
plentiful
reports
link
between
defective
This
treaty
highlights
updated
outlines
modern
innovations
developments
machinery
brains.
therapeutic
nanotherapeutic
strategies
targeting
dysfunction
presented
this
review.
Based
significant
role
diminished
we
suggest
that
application
different
approaches
aimed
at
stimulating
would
be
beneficial
for
or
reducing
induced
Aging and Disease,
Год журнала:
2025,
Номер
unknown, С. 0 - 0
Опубликована: Янв. 1, 2025
Down
syndrome
(DS),
caused
by
trisomy
of
chromosome
21
(HSA21),
is
a
complex
condition
associated
with
neurodevelopmental
impairments
and
accelerated
brain
aging,
often
culminating
in
early-onset
Alzheimer's
disease
(AD).
Central
to
this
aging
mitochondrial
imbalance,
characterized
disrupted
energy
metabolism,
increased
oxidative
stress,
impaired
dynamics,
defective
quality
control
mechanisms
like
mitophagy.
These
abnormalities
exacerbate
neuronal
vulnerability,
driving
cognitive
decline
neurodegeneration.
This
review
examines
the
genetic
biochemical
underpinnings
dysfunction
DS,
focus
on
role
HSA21-encoded
genes.
We
also
highlight
how
dysfunction,
amplified
stress
HSA21
gene
dosage
effects,
converges
cellular
senescence
neuroinflammation
accelerate
Alzheimer-like
pathology
DS.
Finally,
we
discuss
emerging
therapeutic
strategies
targeting
pathways,
which
hold
promise
for
mitigating
neurodegenerative
phenotypes
improving
outcomes
Biomolecules,
Год журнала:
2023,
Номер
13(6), С. 927 - 927
Опубликована: Май 31, 2023
This
Review
emphasizes
the
impact
of
APOE4—the
most
significant
genetic
risk
factor
for
Alzheimer’s
disease
(AD)—on
peripheral
and
neural
effects
starting
in
childhood.
We
discuss
major
mechanistic
players
associated
with
APOE
alleles’
humans
to
understand
their
from
conception
through
all
life
stages
importance
detrimental,
synergistic
environmental
exposures.
APOE4
influences
AD
pathogenesis,
exposure
fine
particulate
matter
(PM2.5),
manufactured
nanoparticles
(NPs),
ultrafine
particles
(UFPs)
combustion
friction
processes
appear
be
contributors
cerebrovascular
dysfunction,
neuroinflammation,
oxidative
stress.
In
context
outdoor
indoor
PM
pollution
burden—as
well
as
Fe,
Ti,
Al
alloys;
Hg,
Cu,
Ca,
Sn,
Si
UFPs/NPs—in
placenta
fetal
brain
tissues,
urban
APOE3
carriers
are
developing
biological
hallmarks
(hyperphosphorylated-tau
(P-tau)
amyloid
beta
42
plaques
(Aβ42)).
Strikingly,
Metropolitan
Mexico
City
(MMC)
young
residents
≤
40
y,
have
4.92
times
higher
suicide
odds
23.6
reaching
Braak
NFT
V
stage
versus
non-carriers.
The
National
Institute
on
Aging
Association
(NIA-AA)
framework
could
serve
test
hypothesis
that
UFPs
NPs
key
stress,
protein
aggregation
misfolding,
faulty
complex
quality
control,
early
damage
cell
membranes
organelles
vascular
cells.
Noninvasive
biomarkers
indicative
P-tau
Aβ42
abnormal
deposits
needed
across
continuum
Among
21.8
million
MMC
residents,
we
potentially
4
at
accelerated
progression.
These
individuals
prime
candidates
neuroprotective
interventional
trials.
is
development
evolving
childhood
highly
polluted
centers
dominated
by
anthropogenic
industrial
sources
pollution.
subjects
development,
neuroprotection
ought
implemented.
Effective
reductions
PM2.5,
UFP,
NP
emissions
urgently
needed.
Disease
prevention
core
public
health
response
physicians-scientist
minority
research
supported.
Journal of Alzheimer s Disease Reports,
Год журнала:
2023,
Номер
7(1), С. 1165 - 1177
Опубликована: Сен. 1, 2023
Alzheimer’s
disease
(AD)
is
a
lethal
neurodegenerative
disorder
characterized
by
severe
brain
pathologies
and
progressive
cognitive
decline.
While
the
exact
cause
of
this
remains
unknown,
emerging
evidence
suggests
that
dysregulation
neurotransmitters
contributes
to
development
AD
pathology
symptoms.
Serotonin,
critical
neurotransmitter
in
brain,
plays
pivotal
role
regulating
various
processes
implicated
neurological
psychiatric
disorders,
including
AD.
Recent
studies
have
shed
light
on
interplay
between
mitochondrial
function
serotonin
regulation
physiology.
In
AD,
there
deficiency
serotonin,
along
with
impairments
function,
particularly
serotoninergic
neurons.
Additionally,
altered
activity
enzymes,
such
as
monoamine
oxidase,
may
contribute
Understanding
intricate
relationship
mitochondria
provides
valuable
insights
into
underlying
mechanisms
identifies
potential
therapeutic
targets
restore
homeostasis
alleviate
This
review
summarizes
recent
advancements
unraveling
connection
emphasizing
their
significance
pathogenesis
underscoring
importance
further
research
area.
Elucidating
dysfunction
will
promote
strategies
for
treatment
prevention
disorder.
Journal of Alzheimer s Disease,
Год журнала:
2024,
Номер
101(s1), С. S155 - S178
Опубликована: Окт. 18, 2024
Alzheimer's
disease
(AD)
is
a
neurodegenerative
disorder
characterized
by
gradual
and
progressive
cognitive
decline
leading
to
dementia.
At
its
core,
the
neuropathological
features
of
AD
include
hallmark
accumulations
amyloid-β
hyperphosphorylated
tau
proteins.
Other
harmful
processes,
such
as
oxidative
stress
inflammation,
contribute
disease's
progression.
This
review
evaluates
role
in
AD,
placing
spotlight
on
disappointing
outcomes
various
antioxidant
clinical
trials.
Several
hypotheses
are
discussed
that
might
elucidate
failures
these
therapies
AD.
Specifically:
1)
The
paradoxical
overlooked
implications
prooxidant
intermediates,
particularly
stemming
from
conventional
antioxidants
like
vitamins
E
C;
2)
challenges
failure
appreciate
issue
bioavailability-epitomized
dictum
"no
on-site
protection,
no
protection"-and
preeminent,
yet
often
ignored,
played
endogenous
enzymes
combating
stress;
3)
influence
unrecognized
etiologies,
latent
infectious
agents
others,
foundational
drivers
AD;
4)
underestimation
complexity
mechanisms
necessity
multi-targeted
therapeutic
approaches,
those
provided
diets;
5)
limitations
trial
designs
fully
capturing
effects
article
also
examines
select
trials
while
highlighting
barriers
pose,
offering
insights
into
potential
overcome
their
marginal
success.
Cells,
Год журнала:
2023,
Номер
12(12), С. 1646 - 1646
Опубликована: Июнь 16, 2023
RalBP1
(Rlip)
is
a
stress-activated
protein
that
believed
to
play
large
role
in
aging
and
neurodegenerative
diseases
such
as
Alzheimer’s
disease
(AD)
other
tauopathies.
The
purpose
of
our
study
was
understand
the
Rlip
mutant
Tau-expressed
immortalized
hippocampal
HT22
cells.
In
current
study,
we
used
Tau
(mTau)-expressed
neurons
cells
transfected
with
Rlip-cDNA
and/or
silenced
RNA,
studied
cell
survival,
mitochondrial
respiration,
function,
immunoblotting,
immunofluorescence
analysis
synaptic
mitophagy
proteins
colocalization
mTau
proteins.
We
found
levels
were
reduced
mTau-HT22
cells,
+
RNA
cells;
on
hand,
increased
observed
cDNA
survival
decreased
RNA-silenced
However,
Rlip-overexpressed
A
significantly
oxygen
consumption
rate
(OCR)
Rlip-HT22
an
even
greater
reduction
OCR
all
groups
overexpress
cDNA.
Mitochondrial
function
defective
further
however,
it
rescued
overexpressed
Synaptic
reductions
these
An
number
mitochondria
length
These
observations
strongly
suggest
deficiency
causes
oxidative
stress/mitochondrial
dysfunction
overexpression
reverses
defects.
Overall,
findings
revealed
promising
new
target
for
aging,
AD,
tauopathies/neurological
diseases.
