Current Opinion in Structural Biology,
Journal Year:
2024,
Volume and Issue:
85, P. 102776 - 102776
Published: Feb. 8, 2024
The
complex
molecular
mechanism
and
pathophysiology
of
Alzheimer's
disease
(AD)
limits
the
development
effective
therapeutics
or
prevention
strategies.
Artificial
Intelligence
(AI)-guided
drug
discovery
combined
with
genetics/multi-omics
(genomics,
epigenomics,
transcriptomics,
proteomics,
metabolomics)
analysis
contributes
to
understanding
precision
medicine
disease,
including
AD
AD-related
dementia.
In
this
review,
we
summarize
AI-driven
methodologies
for
AD-agnostic
development,
de
novo
design,
virtual
screening,
prediction
drug-target
interactions,
all
which
have
shown
potentials.
particular,
AI-based
repurposing
emerges
as
a
compelling
strategy
identify
new
indications
existing
drugs
AD.
We
provide
several
emerging
targets
from
human
genetics
multi-omics
findings
highlight
recent
technologies
their
applications
in
using
prototypical
example.
closing,
discuss
future
challenges
directions
other
neurodegenerative
diseases.
Signal Transduction and Targeted Therapy,
Journal Year:
2022,
Volume and Issue:
7(1)
Published: Dec. 16, 2022
Aging
is
a
gradual
and
irreversible
pathophysiological
process.
It
presents
with
declines
in
tissue
cell
functions
significant
increases
the
risks
of
various
aging-related
diseases,
including
neurodegenerative
cardiovascular
metabolic
musculoskeletal
immune
system
diseases.
Although
development
modern
medicine
has
promoted
human
health
greatly
extended
life
expectancy,
aging
society,
variety
chronic
diseases
have
gradually
become
most
important
causes
disability
death
elderly
individuals.
Current
research
on
focuses
elucidating
how
endogenous
exogenous
stresses
(such
as
genomic
instability,
telomere
dysfunction,
epigenetic
alterations,
loss
proteostasis,
compromise
autophagy,
mitochondrial
cellular
senescence,
stem
exhaustion,
altered
intercellular
communication,
deregulated
nutrient
sensing)
participate
regulation
aging.
Furthermore,
thorough
pathogenesis
to
identify
interventions
that
promote
longevity
caloric
restriction,
microbiota
transplantation,
nutritional
intervention)
clinical
treatment
methods
for
(depletion
senescent
cells,
therapy,
antioxidative
anti-inflammatory
treatments,
hormone
replacement
therapy)
could
decrease
incidence
turn
healthy
longevity.
Theranostics,
Journal Year:
2023,
Volume and Issue:
13(2), P. 736 - 766
Published: Jan. 1, 2023
Cellular
mitophagy
means
that
cells
selectively
wrap
and
degrade
damaged
mitochondria
through
an
autophagy
mechanism,
thus
maintaining
intracellular
homeostasis.In
recent
years,
has
received
increasing
attention
as
a
research
hotspot
related
to
the
pathogenesis
of
clinical
diseases,
such
neurodegenerative
cardiovascular
cancer,
metabolic
so
on.It
been
found
regulation
may
become
new
direction
for
treatment
some
diseases.In
addition,
numerous
small
molecule
modulators
have
also
reported,
which
provides
opportunities
comprehend
procedure
potential
therapeutic
development.Taken
together,
in
this
review,
we
summarize
current
understanding
mechanism
mitophagy,
discuss
roles
its
relationship
with
introduce
existing
small-molecule
pharmacological
further
highlight
significance
their
development.
Signal Transduction and Targeted Therapy,
Journal Year:
2023,
Volume and Issue:
8(1)
Published: Aug. 16, 2023
Abstract
Mitochondria
are
dynamic
organelles
with
multiple
functions.
They
participate
in
necrotic
cell
death
and
programmed
apoptotic,
crucial
for
metabolism
survival.
Mitophagy
serves
as
a
cytoprotective
mechanism
to
remove
superfluous
or
dysfunctional
mitochondria
maintain
mitochondrial
fine-tuning
numbers
balance
intracellular
homeostasis.
Growing
evidences
show
that
mitophagy,
an
acute
tissue
stress
response,
plays
important
role
maintaining
the
health
of
network.
Since
timely
removal
abnormal
is
essential
survival,
cells
have
evolved
variety
mitophagy
pathways
ensure
can
be
activated
time
under
various
environments.
A
better
understanding
diseases
treatment
therapeutic
target
design.
In
this
review,
we
summarize
molecular
mechanisms
mitophagy-mediated
elimination,
how
maintains
homeostasis
at
system
levels
organ,
what
alterations
related
development
diseases,
including
neurological,
cardiovascular,
pulmonary,
hepatic,
renal
disease,
etc.,
recent
advances.
Finally,
potential
clinical
applications
outline
conditions
regulators
enter
trials.
Research
advances
signaling
transduction
will
developing
new
strategies
precision
medicine.
Aging,
Journal Year:
2022,
Volume and Issue:
14(16), P. 6829 - 6839
Published: Aug. 29, 2022
Aging
|
doi:10.18632/aging.204248.
Tomas
Schmauck-Medina,
Adrian
Molière,
Sofie
Lautrup,
Jianying
Zhang,
Stefan
Chlopicki,
Helena
Borland
Madsen,
Shuqin
Cao,
Casper
Soendenbroe,
Els
Mansell,
Mark
Bitsch
Vestergaard,
Zhiquan
Li,
Yosef
Shiloh,
Patricia
L.
Opresko,
Jean-Marc
Egly,
Thomas
Kirkwood,
Eric
Verdin,
Vilhelm
A.
Bohr,
Lynne
S.
Cox,
Tinna
Stevnsner,
Lene
Juel
Rasmussen,
Evandro
F.
Fang
Molecular Psychiatry,
Journal Year:
2022,
Volume and Issue:
28(1), P. 202 - 216
Published: June 3, 2022
Abstract
Mitochondrial
dysfunctions
are
central
players
in
Alzheimer’s
disease
(AD).
In
addition,
impairments
mitophagy,
the
process
of
selective
mitochondrial
degradation
by
autophagy
leading
to
a
gradual
accumulation
defective
mitochondria,
have
also
been
reported
occur
AD.
We
provide
an
updated
overview
recent
discoveries
and
advancements
on
mitophagic
molecular
AD-derived
fluids
cells
as
well
AD
brains.
discuss
studies
using
cellular
animal
models
that
unraveled
contribution
relevant
AD-related
proteins
(Tau,
Aβ,
APP-derived
fragments
APOE)
mitophagy
failure.
accordance
with
important
role
impaired
AD,
we
report
various
therapeutic
strategies
aiming
at
stimulating
summarize
benefits
these
potential
human
clinical
trials.
