Cell Biochemistry and Function,
Год журнала:
2024,
Номер
42(8)
Опубликована: Дек. 1, 2024
ABSTRACT
Autophagy
is
an
essential
intracellular
degradation
system
responsible
for
delivering
cytoplasmic
components
to
lysosomes.
Within
this
intricate
process,
optineurin
(OPTN),
autophagy
receptor,
has
attracted
extensive
attention
due
its
multifaceted
roles
in
the
process.
OPTN
regulated
by
various
posttranslational
modifications
and
actively
participates
numerous
signaling
pathways
cellular
processes.
By
exploring
regulatory
mechanism
of
modification,
we
can
further
understand
critical
role
protein
modification
biological
progress,
such
as
autophagy.
Additionally,
implicated
many
human
diseases,
including
rheumatoid
arthritis,
osteoporosis,
infectious
diseases.
And
delve
into
inflammatory
clarify
how
it
regulates
diseases
cancer.
We
aim
enhance
understanding
OPTN's
functions
processes
implications
pathogenesis
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 19, 2024
Cellular
senescence
is
a
major
contributor
to
aging-related
degenerative
diseases,
including
Alzheimer's
disease
(AD)
but
much
less
known
on
the
key
cell
types
and
pathways
driving
mechanisms
of
in
brain.
We
hypothesized
that
dysregulated
cholesterol
metabolism
central
cellular
AD.
analyzed
whole
transcriptomic
data
utilized
single-cell
RNA
seq
integration
techniques
unveil
convoluted
cell-type-specific
sub-cell-type-state-specific
pathologies
AD
using
both
ROSMAP
Sea-AD
datasets.
identified
microglia
are
components
associated
phenotypes
snRNA-seq
(982,384
nuclei
from
postmortem
prefrontal
cortex
239
188
non-AD)
among
non-neuron
types.
homeostatic,
inflammatory,
phagocytic,
lipid
processing
neuronal
surveillance
states
were
with
(152,459
six
regions
brain
tissue
138
early
AD,
79
late
226
control
subject)
(82,486
42
dementia,
no
dementia
5
reference
subjects)
via
integrative
analysis,
which
preserves
meaningful
biological
information
across
assessed
top
bioprocesses
mitochondrial,
apoptosis,
oxidative
stress,
ER
endosomes,
lysosomes
systems.
Specifically,
we
found
senescent
have
altered
related
cholesterol.
discovered
three
gene
co-expression
modules,
represent
specific
signatures
brains.
To
validate
these
findings,
activation
was
analysis
iMGs
(microglia
induced
iPSCs)
exposed
myelin,
Abeta,
synaptosomes
(56,454
two
replicates
untreated
four
treated
groups).
In
vivo
preserved
after
treatment
pathological
substrates
iMGs.
This
study
provides
first
evidence
dysregulation
driver
Targeting
an
attractive
strategy
slow
down
progression.
Cell Biochemistry and Function,
Год журнала:
2024,
Номер
42(8)
Опубликована: Дек. 1, 2024
ABSTRACT
Autophagy
is
an
essential
intracellular
degradation
system
responsible
for
delivering
cytoplasmic
components
to
lysosomes.
Within
this
intricate
process,
optineurin
(OPTN),
autophagy
receptor,
has
attracted
extensive
attention
due
its
multifaceted
roles
in
the
process.
OPTN
regulated
by
various
posttranslational
modifications
and
actively
participates
numerous
signaling
pathways
cellular
processes.
By
exploring
regulatory
mechanism
of
modification,
we
can
further
understand
critical
role
protein
modification
biological
progress,
such
as
autophagy.
Additionally,
implicated
many
human
diseases,
including
rheumatoid
arthritis,
osteoporosis,
infectious
diseases.
And
delve
into
inflammatory
clarify
how
it
regulates
diseases
cancer.
We
aim
enhance
understanding
OPTN's
functions
processes
implications
pathogenesis
