Cells,
Год журнала:
2022,
Номер
11(17), С. 2660 - 2660
Опубликована: Авг. 27, 2022
In
the
current
study,
for
first
time,
we
study
mitophagy
enhancer
urolithin
A
and
a
combination
of
A+green
tea
extract
EGCG
against
human
Aβ
peptide-induced
mitochondrial
synaptic,
dendritic,
inflammatory
toxicities
behavioral
changes
in
humanized
homozygous
amyloid
beta
knockin
(hAbKI)
mice
late-onset
Alzheimer's
disease
(AD).
Our
findings
reveal
significantly
increased
positive
effects
treatment
A+EGCG
hAbKI
phenotypic
including
motor
coordination,
locomotion/exploratory
activity,
spatial
learning
working
memory.
mRNA
protein
levels
fusion,
autophagy
genes
were
upregulated,
fission
are
downregulated
combine
mice;
however,
effect
is
stronger
combined
treatment.
Immunofluorescence
analysis
hippocampal
brain
sections
shows
similar
levels.
Mitochondrial
dysfunction
reduced
both
groups,
but
reduction
observed
Dendritic
spines
lengths
The
fragmented
number
mitochondria
reduced,
length
increased,
mitophagosomal
formations
(Aβ)
40
Aβ42
treatments,
higher
These
observations
suggest
that
protective
toxicities;
effective
stronger,
indicating
therapy
promising
to
treat
AD
patients.
International Journal of Molecular Sciences,
Год журнала:
2022,
Номер
23(21), С. 12841 - 12841
Опубликована: Окт. 25, 2022
Alzheimer’s
disease
(AD)
is
the
leading
cause
of
dementia
in
elderly
people.
Amyloid
beta
(Aβ)
deposits
and
neurofibrillary
tangles
are
major
pathological
features
an
brain.
These
proteins
highly
expressed
nerve
cells
found
most
tissues.
Tau
primarily
provides
stabilization
to
microtubules
part
axons
dendrites.
However,
tau
a
state
becomes
hyperphosphorylated,
causing
dysfunction
synaptic
impairment
degeneration
neurons.
This
article
presents
summary
role
tau,
phosphorylated
(p-tau)
AD,
other
tauopathies.
Tauopathies,
including
Pick’s
disease,
frontotemporal
dementia,
corticobasal
degeneration,
argyrophilic
grain
progressive
supranuclear
palsy,
Huntington’s
result
misprocessing
accumulation
within
neuronal
glial
cells.
also
focuses
on
current
research
post-translational
modifications
genetics
pathology,
tauopathies
development
new
drugs
targeting
p-tau,
therapeutics
for
treating
possibly
preventing
Cells,
Год журнала:
2022,
Номер
11(15), С. 2262 - 2262
Опубликована: Июль 22, 2022
Autophagy
is
a
highly
conserved
lysosomal
degradation
pathway
active
at
basal
levels
in
all
cells.
However,
under
stress
conditions,
such
as
lack
of
nutrients
or
trophic
factors,
it
works
survival
mechanism
that
allows
the
generation
metabolic
precursors
for
proper
functioning
cells
until
are
available.
Neurons,
post-mitotic
cells,
depend
largely
on
autophagy
to
maintain
cell
homeostasis
get
rid
damaged
and/or
old
organelles
and
misfolded
aggregated
proteins.
Therefore,
dysfunction
this
process
contributes
pathologies
many
human
diseases.
Furthermore,
during
differentiation
development.
In
review,
we
describe
current
knowledge
different
pathways,
molecular
mechanisms,
factors
induce
it,
regulation
mammalian
autophagy.
We
also
discuss
its
relevant
role
development
disease.
Finally,
here
summarize
several
investigations
demonstrating
autophagic
abnormalities
have
been
considered
underlying
reasons
diseases,
including
liver
disease,
cardiovascular,
cerebrovascular
neurodegenerative
neoplastic
cancers,
and,
more
recently,
infectious
SARS-CoV-2
caused
COVID-19
Journal of Neuroinflammation,
Год журнала:
2022,
Номер
19(1)
Опубликована: Окт. 6, 2022
Abstract
Alzheimer's
disease
(AD)
is
the
most
common
neurodegenerative
in
elderly
globally.
Emerging
evidence
has
demonstrated
microglia-driven
neuroinflammation
as
a
key
contributor
to
onset
and
progression
of
AD,
however,
mechanisms
that
mediate
remain
largely
unknown.
Recent
studies
have
suggested
mitochondrial
dysfunction
including
DNA
(mtDNA)
damage,
metabolic
defects,
quality
control
(QC)
disorders
precedes
microglial
activation
subsequent
neuroinflammation.
Therefore,
an
in-depth
understanding
relationship
between
AD
important
unveil
pathogenesis
develop
effective
approaches
for
early
diagnosis
treatment.
In
this
review,
we
summarized
current
progress
roles
mtDNA,
metabolism,
QC
changes
provide
comprehensive
thoughts
targeting
mitochondria
potential
therapeutic
strategies
AD.
Life,
Год журнала:
2024,
Номер
14(2), С. 196 - 196
Опубликована: Янв. 30, 2024
Alzheimer’s
disease
(AD)
is
a
progressive
and
incurable
neurodegenerative
disorder
that
primarily
affects
persons
aged
65
years
above.
It
causes
dementia
with
memory
loss
deterioration
in
thinking
language
skills.
AD
characterized
by
specific
pathology
resulting
from
the
accumulation
brain
of
extracellular
plaques
amyloid-β
intracellular
tangles
phosphorylated
tau.
The
importance
mitochondrial
dysfunction
pathogenesis,
while
previously
underrecognized,
now
more
appreciated.
Mitochondria
are
an
essential
organelle
involved
cellular
bioenergetics
signaling
pathways.
Mitochondrial
processes
crucial
for
synaptic
activity
such
as
mitophagy,
trafficking,
fission,
fusion
dysregulated
brain.
Excess
fission
fragmentation
yield
mitochondria
low
energy
production.
Reduced
glucose
metabolism
also
observed
hypometabolic
state,
particularly
temporo-parietal
regions.
This
review
addresses
multiple
ways
which
abnormal
structure
function
contribute
to
AD.
Disruption
electron
transport
chain
ATP
production
neurotoxic
because
cells
have
disproportionately
high
demands.
In
addition,
oxidative
stress,
extremely
damaging
nerve
cells,
rises
dramatically
dyshomeostasis.
Restoring
health
may
be
viable
approach
treatment.
Human Molecular Genetics,
Год журнала:
2021,
Номер
31(3), С. 423 - 439
Опубликована: Сен. 8, 2021
The
purpose
of
our
study
is
to
determine
the
protective
effects
mitophagy
enhancers
against
mutant
APP
and
amyloid
beta
(Aβ)-induced
mitochondrial
synaptic
toxicities
in
Alzheimer's
disease
(ad).
Over
two
decades
research
from
lab
others
revealed
that
abnormalities
are
largely
involved
pathogenesis
both
early-onset
late-onset
ad.
Emerging
studies
impaired
clearance
dead
or
dying
mitochondria
an
early
event
process.
Based
on
these
changes,
it
has
been
proposed
potential
therapeutic
candidates
treat
patients
with
In
current
study,
we
optimized
doses
urolithin
A,
actinonin,
tomatidine,
nicotinamide
riboside
immortalized
mouse
primary
hippocampal
(HT22)
neurons.
We
transfected
HT22
cells
cDNA
treated
assessed
mRNA
protein
levels
dynamics,
biogenesis,
genes,
cell
survival;
respiration
mAPP-HT22
untreated
enhancers.
also
morphology
Mutant
APP-HT22
showed
increased
fission,
decreased
fusion,
&
reduced
survival
defective
respiration,
excessively
fragmented
length
mitochondria.
However,
events
were
reversed
mitophagy-enhancers-treated
cells.
Cell
was
significantly
increased,
genes
number
reduced,
fragmentation
Further,
A
strongest
Aβ-induced
findings,
cautiously
propose
promising
drugs
International Journal of Molecular Sciences,
Год журнала:
2021,
Номер
22(21), С. 11520 - 11520
Опубликована: Окт. 26, 2021
Alzheimer’s
disease
(AD)
is
a
major
cause
of
dementia
in
older
adults
and
fast
becoming
societal
economic
burden
due
to
an
increase
life
expectancy.
Age
seems
be
the
factor
driving
AD,
currently,
only
symptomatic
treatments
are
available.
AD
has
complex
etiology,
although
mitochondrial
dysfunction,
oxidative
stress,
inflammation,
metabolic
abnormalities
have
been
widely
deeply
investigated
as
plausible
mechanisms
for
its
neuropathology.
Aβ
plaques
hyperphosphorylated
tau
aggregates,
along
with
cognitive
deficits
behavioral
problems,
hallmarks
disease.
Restoration
bioenergetics,
prevention
diet
exercise
seem
effective
reducing
ameliorating
learning
memory
problems.
Many
mitochondria-targeted
antioxidants
tested
currently
development.
However,
larger
streamlined
clinical
studies
needed
provide
hard
evidence
benefits
AD.
This
review
discusses
causative
factors,
well
potential
therapeutics
employed
treatment
