Mitochondria-Targeted Biomaterials-Regulating Macrophage Polarization Opens New Perspectives for Disease Treatment
International Journal of Nanomedicine,
Год журнала:
2025,
Номер
Volume 20, С. 1509 - 1528
Опубликована: Фев. 1, 2025
Abstract:
Macrophage
immunotherapy
is
an
emerging
therapeutic
approach
designed
for
modulating
the
immune
response
to
alleviate
disease
symptoms.
The
balance
between
pro-inflammatory
and
anti-inflammatory
macrophages
plays
a
pivotal
role
in
progression
of
inflammatory
diseases.
Mitochondria,
often
referred
as
"power
plants"
cell,
are
essential
organelles
responsible
critical
functions
such
energy
metabolism,
material
synthesis,
signal
transduction.
functional
state
mitochondria
closely
linked
macrophage
polarization,
prompting
interest
strategies
that
target
regulate
this
process.
To
end,
biomaterials
with
excellent
targeting
capabilities
effective
properties
have
been
developed
influence
mitochondrial
function
polarization.
However,
comprehensive
summary
biomaterial-driven
modulation
control
phenotypes
still
lacking.
This
review
highlights
polarization
discusses
mediated
by
biomaterials,
including
mitochondria-targeted
biomaterials.
Finally,
prospects
challenges
use
these
explored,
emphasizing
their
potential
be
translated
clinic.
It
anticipated
will
serve
valuable
resource
materials
scientists
clinicians
development
next-generation
Keywords:
macrophages,
Язык: Английский
Chuangxiong-Danggui Herb Pair Alleviated Cognitive Deficits of App/Ps1 Mice by Promoting Fundc1-Mediated Mitophagy
Опубликована: Янв. 1, 2025
Background:
Disruption
of
receptor-mediated
mitophagy
contributes
to
neuronal
damage
in
AD.
Chuangxiong-Danggui
herb
pair
(CDHP)
is
classic
herbal
applied
treating
neurodegenerative
diseases
like
AD,
ALS,
PD.
Studies
have
indicated
the
neuroprotective
effects
CDHP,
underlying
mechanisms
by
which
CDHP
attenuates
impairment
AD
remains
be
elucidated.PurposeThe
objective
this
work
was
investigate
anti-AD
mechanism
APP/PS1
mice
mainly
based
on
FUNDC1-mediated
mitophagy.MethodsBehavioral
assessments
were
conducted
C57BL/6J
and
following
treatment,
alongside
an
evaluation
morphology
hippocampal
region.
In
vitro,
HT-22
cells
induced
Aβ25-35
before
treated
with
CDHP.
The
investigated
using
transmission
electron
microscopy,
Golgi
staining,
immunofluorescence,
siRNA,
Western
blot
analysis.ResultsResults
from
passive
avoidance
test
MWM
that
significantly
mitigated
cognitive
deficits
mice,
accompanied
a
reduction
pathological
CA1
CA3
regions
hippocampus.
Further
testing
found
significant
dendritic
spines
density
rescued
protein
synaptophysin
PSD-95
elevated
group,
while
Aβ
plaques
deposition
reduced.
Simultaneously,
markedly
inhibits
apoptosis
decreased
levels
Cleaved
Caspase-12
enhanced
expression
Bcl-2/Bax
both
vivo
vitro.
Additionally,
improved
mitochondrial
function
model
decreasing
abnormal
mitochondria
increasing
COXIV.
TEM
results
revealed
clear
mitophagy-autophagosomes
nearly
absent
p62
LC3B
treatment.
Furthermore,
increased
FUNDC1
transgenic
or
AD-like
cell
model,
luckily,
it
restoring
II/I
ratio
vitro.ConclusionThe
findings
suggest
dysfunction
enhancing
reduced
injury.
Язык: Английский
Quality control of mitochondrial nucleoids
Trends in Cell Biology,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 1, 2025
Язык: Английский
A positive feedback loop between SMAD3 and PINK1 in regulation of mitophagy
Cell Discovery,
Год журнала:
2025,
Номер
11(1)
Опубликована: Март 11, 2025
Abstract
PTEN-induced
kinase-1
(PINK1)
is
a
crucial
player
in
selective
clearance
of
damaged
mitochondria
via
the
autophagy-lysosome
pathway,
process
termed
mitophagy.
Previous
studies
on
PINK1
mainly
focused
its
post-translational
modifications,
while
transcriptional
regulation
much
less
understood.
Herein,
we
reported
novel
mechanism
control
transcription
by
SMAD
Family
Member
3
(SMAD3),
an
essential
component
transforming
growth
factor
beta
(TGFβ)-SMAD
signaling
pathway.
First,
observed
that
mitochondrial
depolarization
promotes
transcription,
and
SMAD3
likely
to
be
nuclear
mediating
transcription.
Intriguingly,
positively
transactivates
independent
canonical
TGFβ
components,
such
as
TGFβ-R1,
SMAD2
or
SMAD4.
Second,
found
activates
PINK1-mediated
phosphorylation
at
serine
423/425.
Therefore,
constitute
positive
feedforward
loop
Finally,
activation
provides
important
pro-survival
signal,
depletion
sensitizes
cells
cell
death
caused
stress.
In
summary,
our
findings
identify
non-canonical
function
mitophagy
feedback
activation.
Understanding
this
regulatory
deeper
insight
into
pathological
pathogenesis
neurodegenerative
diseases
Parkinson's
disease.
Язык: Английский
Parkinson’s Disease: The Neurodegenerative Enigma Under the “Undercurrent” of Endoplasmic Reticulum Stress
International Journal of Molecular Sciences,
Год журнала:
2025,
Номер
26(7), С. 3367 - 3367
Опубликована: Апрель 3, 2025
Parkinson's
disease
(PD),
a
prevalent
neurodegenerative
disorder,
demonstrates
the
critical
involvement
of
endoplasmic
reticulum
stress
(ERS)
in
its
pathogenesis.
This
review
comprehensively
examines
role
and
molecular
mechanisms
ERS
PD.
represents
cellular
response
triggered
by
imbalances
(ER)
homeostasis,
induced
factors
such
as
hypoxia
misfolded
protein
aggregation,
which
activate
unfolded
(UPR)
through
inositol-requiring
enzyme
1
(IRE1),
kinase
R-like
(PERK),
activating
transcription
factor
6
(ATF6)
pathways.
Clinical,
animal
model,
studies
have
consistently
demonstrated
strong
association
between
PD
ERS.
Abnormal
expression
ERS-related
molecules
patients'
brains
cerebrospinal
fluid
(CSF)
correlates
with
progression.
In
models
(e.g.,
Drosophila
mice),
inhibition
alleviates
dopaminergic
neuronal
damage.
Cellular
experiments
reveal
that
PD-mimicking
pathological
conditions
induce
ERS,
while
interactions
mitochondrial
dysfunction
promote
apoptosis.
Mechanistically,
(1)
aggregation
α-synuclein
(α-syn)
mutually
reinforce
neuron
damage;
(2)
leucine-rich
repeat
2
(LRRK2)
gene
mutations
thrombospondin-1
(THBS1)/transforming
growth
beta
(TGF-β1)
interactions;
(3)
Parkin
PTEN-induced
(PINK1)
regulate
Furthermore,
interacts
dysfunction,
oxidative
stress,
neuroinflammation
to
exacerbate
injury.
Emerging
therapeutic
strategies
show
significant
potential,
including
artificial
intelligence
(AI)-assisted
drug
design
targeting
pathways
precision
medicine
approaches
exploring
non-pharmacological
interventions
personalized
electroacupuncture.
Future
research
should
focus
on
elucidating
identifying
novel
targets
develop
more
effective
treatments
for
patients,
ultimately
improving
their
quality
life.
Язык: Английский
A novel dual CCK/ GLP-1 receptor agonist ameliorates cognitive impairment in 5 × FAD mice by modulating mitophagy via the PINK1/Parkin pathway
International Immunopharmacology,
Год журнала:
2025,
Номер
154, С. 114612 - 114612
Опубликована: Апрель 6, 2025
Язык: Английский
Presynapses are mitophagy pit stops that prevent axon degeneration
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 9, 2024
Abstract
Defects
in
neuronal
mitophagy
have
been
linked
to
neurodegenerative
diseases
including
Parkinson’s
disease.
However,
despite
the
importance
of
homeostasis,
mechanistic
basis
for
neurodegeneration
when
is
defective
unclear.
Here,
using
human
neurons,
we
discover
that
presynapses
are
pit
stops
damaged
axonal
mitochondria.
We
show
while
mitochondrial
damage
and
PINK1/Parkin
activation
events
distributed
throughout
axons,
initiation
autophagosome
formation
restricted
presynapses,
which
contain
machineries
required
mitophagy.
Being
primary
sites
mitophagy,
were
vulnerable
was
defective.
observed
local
cytochrome
c
release
within
from
an
accumulation
This
resulted
downstream
degradative
caspase
activation,
defining
a
mechanism
neurodegeneration.
Pharmacological
rescue
axon
degeneration
achieved
through
synthetic
upregulation
receptor
mediated
with
clinically
approved
compound
Roxadustat,
revealing
potential
therapeutic
avenue
Язык: Английский
Targeting mitochondria by lipid-selenium conjugate drug results in malate/fumarate exhaustion and induces mitophagy-mediated necroptosis suppression
International Journal of Biological Sciences,
Год журнала:
2024,
Номер
20(14), С. 5793 - 5811
Опубликована: Окт. 28, 2024
Atherosclerosis
(AS)
is
a
chronic
vascular
disease
primarily
affecting
large
and
medium-sized
arteries
involves
various
complex
pathological
mechanisms
factors.
Previous
studies
have
demonstrated
close
association
between
atherosclerosis
inflammatory
damage,
metabolic
disorders,
gut
microbiota.
It
also
closely
linked
to
several
cellular
processes,
such
as
endothelial
cell
pyroptosis,
ferroptosis,
mitophagy,
mitochondrial
dynamics,
biogenesis.
Mitophagy
has
been
recognized
previously
unexplored
mechanism
contributing
injury
in
atherosclerosis.
Our
study
aims
further
elucidate
the
potential
relationship
AS-induced
mitophagy
dysfunction
interaction
of
TMBIM6
NDUFS4.
Data
from
that
AS
mice
was
associated
with
substantial
activation
oxidative
stress
along
marked
reduction
expression
increased
fission,
leading
homeostasis
disruption.
However,
under
pharmacological
intervention,
levels
significantly
increased,
fission
notably
reduced,
damage
were
suppressed,
while
necroptotic
pathways
cells
blocked.
Interestingly,
deletion
or
NDUFS4
animal
models
lines
markedly
impaired
therapeutic
effects
drug,
disrupting
its
regulation
re-emergence
responses
damage.
Metabolomics
analysis
revealed
autophagy
plays
pivotal
regulatory
role
during
drug
intervention
after
genetic
modification
The
(macroautophagy/mitophagy)
alleviated
negative
induced
by
lipid
cells,
likely
TMBIM6-NDUFS4
axis.
Subsequent
gene
experiments
knocking
out
negates
on
lipid-induced
function.
In
summary,
our
research
reveals
phenotypic
through
influenced
Pharmacological
can
restore
regulating
via
pathway.
This
novel
insight
suggests
may
serve
key
target
for
Язык: Английский
Ailanthone blocks mitophagy to promote mtDNA leakage through BAX-BAK1 pores and suppress hepatocellular carcinoma cell proliferation
Frontiers in Pharmacology,
Год журнала:
2024,
Номер
15
Опубликована: Дек. 11, 2024
Hepatocellular
carcinoma
(HCC),
the
third
leading
cancer
mortality
worldwide,
shows
rising
incidence.
The
mitochondria
in
HCC
cells
are
prone
to
damage
from
metabolic
stress
and
oxidative
stress,
necessitating
heightened
mitophagy
for
mitochondrial
homeostasis
cell
survival.
Thus,
inhibition
is
a
promising
therapy.
traditional
Chinese
medicinal
herb
ailanthone
have
proved
promote
dysfunction
inhibits
HCC.
However,
underlying
mechanism
remains
unclear.
Язык: Английский
Glucose-6-phosphate dehydrogenase regulates mitophagy by maintaining PINK1 stability
Life Metabolism,
Год журнала:
2024,
Номер
4(1)
Опубликована: Дек. 13, 2024
Abstract
Glucose-6-phosphate
dehydrogenase
(G6PD)
is
the
rate-limiting
enzyme
in
pentose
phosphate
pathway
(PPP)
glycolysis.
Glucose
metabolism
closely
implicated
regulation
of
mitophagy,
a
selective
form
autophagy
for
degradation
damaged
mitochondria.
The
PPP
and
its
key
enzymes
such
as
G6PD
possess
important
metabolic
functions,
including
biosynthesis
maintenance
intracellular
redox
balance,
while
their
implication
mitophagy
largely
unknown.
Here,
via
whole-genome
CRISPR-Cas9
screening,
we
identified
that
regulates
PINK1
(phosphatase
tensin
homolog
[PTEN]-induced
kinase
1)-Parkin-mediated
mitophagy.
function
was
verified
multiple
approaches.
deletion
significantly
inhibited
which
can
be
rescued
by
reconstitution.
Intriguingly,
catalytic
activity
required,
known
functions
per
se
are
not
involved
regulation.
Importantly,
found
portion
localized
at
mitochondria
where
it
interacts
with
PINK1.
resulted
an
impairment
stabilization
subsequent
inhibition
ubiquitin
phosphorylation,
starting
point
Finally,
lower
cell
viability
upon
mitochondrial
depolarization,
indicating
physiological
G6PD-mediated
response
to
stress.
In
summary,
our
study
reveals
novel
role
positive
regulator
bridges
several
cellular
processes,
namely
glucose
metabolism,
homeostasis,
quality
control.
Язык: Английский