Mitochondrial DNA leakage: underlying mechanisms and therapeutic implications in neurological disorders
Journal of Neuroinflammation,
Год журнала:
2025,
Номер
22(1)
Опубликована: Фев. 7, 2025
Mitochondrial
dysfunction
is
a
pivotal
instigator
of
neuroinflammation,
with
mitochondrial
DNA
(mtDNA)
leakage
as
critical
intermediary.
This
review
delineates
the
intricate
pathways
leading
to
mtDNA
release,
which
include
membrane
permeabilization,
vesicular
trafficking,
disruption
homeostatic
regulation,
and
abnormalities
in
dynamics.
The
escaped
activates
cytosolic
sensors,
especially
cyclic
gmp-amp
synthase
(cGAS)
signalling
inflammasome,
initiating
neuroinflammatory
cascades
via
pathways,
exacerbating
spectrum
neurological
pathologies.
therapeutic
promise
targeting
discussed
detail,
underscoring
necessity
for
multifaceted
strategy
that
encompasses
preservation
homeostasis,
prevention
leakage,
reestablishment
dynamics,
inhibition
activation
sensors.
Advancing
our
understanding
complex
interplay
between
neuroinflammation
imperative
developing
precision
interventions
disorders.
Язык: Английский
Neurovascular unit, neuroinflammation and neurodegeneration markers in brain disorders
Frontiers in Cellular Neuroscience,
Год журнала:
2024,
Номер
18
Опубликована: Окт. 25, 2024
Neurovascular
unit
(NVU)
inflammation
via
activation
of
glial
cells
and
neuronal
damage
plays
a
critical
role
in
neurodegenerative
diseases.
Though
the
exact
mechanism
disease
pathogenesis
is
not
understood,
certain
biomarkers
provide
valuable
insight
into
pathogenesis,
severity,
progression
therapeutic
efficacy.
These
markers
can
be
used
to
assess
pathophysiological
status
brain
including
neurons,
astrocytes,
microglia,
oligodendrocytes,
specialized
microvascular
endothelial
cells,
pericytes,
NVU,
blood-brain
barrier
(BBB)
disruption.
Damage
or
derangements
tight
junction
(TJ),
adherens
(AdJ),
gap
(GJ)
components
BBB
lead
increased
permeability
neuroinflammation
various
disorders
disorders.
Thus,
neuroinflammatory
evaluated
blood,
cerebrospinal
fluid
(CSF),
tissues
determine
neurological
progression,
responsiveness.
Chronic
common
age-related
Alzheimer's
(AD),
Parkinson's
(PD),
dementia.
Neurotrauma/traumatic
injury
(TBI)
also
leads
acute
chronic
responses.
The
expression
some
may
altered
many
years
even
decades
before
onset
In
this
review,
we
discuss
neuroinflammation,
neurodegeneration
associated
with
disorders,
especially
those
neurovascular
pathologies.
CSF,
tissues.
Neurofilament
light
(NfL),
ubiquitin
C-terminal
hydrolase-L1
(UCHL1),
fibrillary
acidic
protein
(GFAP),
Ionized
calcium-binding
adaptor
molecule
1
(Iba-1),
transmembrane
119
(TMEM119),
aquaporin,
endothelin-1,
platelet-derived
growth
factor
receptor
beta
(PDGFRβ)
are
important
markers.
Recent
BBB-on-a-chip
modeling
offers
promising
potential
for
providing
an
in-depth
understanding
neurotherapeutics.
Integration
these
clinical
practice
could
potentially
enhance
early
diagnosis,
monitor
improve
outcomes.
Язык: Английский
Methamphetamine Increases Tubulo-Vesicular Areas While Dissipating Proteins from Vesicles Involved in Cell Clearance
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(17), С. 9601 - 9601
Опубликована: Сен. 4, 2024
Cytopathology
induced
by
methamphetamine
(METH)
is
reminiscent
of
degenerative
disorders
such
as
Parkinson’s
disease,
and
it
characterized
membrane
organelles
arranged
in
tubulo-vesicular
structures.
These
areas,
appearing
clusters
vesicles,
have
never
been
defined
concerning
the
presence
specific
organelles.
Therefore,
present
study
aimed
to
identify
relative
absolute
area
membrane-bound
following
a
moderate
dose
(100
µM)
METH
administered
catecholamine-containing
PC12
cells.
Organelles
antigens
were
detected
immunofluorescence,
they
further
quantified
plain
electron
microscopy
situ
stoichiometry.
This
analysis
indicated
an
increase
autophagosomes
damaged
mitochondria
along
with
decrease
lysosomes
healthy
mitochondria.
Following
METH,
severe
dissipation
hallmark
proteins
from
their
own
vesicles
was
measured.
In
fact,
amounts
LC3
p62
reduced
within
autophagy
vacuoles
compared
whole
cytosol.
Similarly,
LAMP1
Cathepsin-D
reduced.
findings
suggest
loss
compartmentalization
confirm
competence
cell
clearing
during
catecholamine
degeneration.
Such
entropy
consistent
energy
stores,
which
routinely
govern
appropriate
subcellular
compartmentalization.
Язык: Английский