Journal of Pharmacological Sciences,
Journal Year:
2024,
Volume and Issue:
155(2), P. 52 - 62
Published: March 27, 2024
The
ubiquitin-proteasome
system
(UPS)
is
a
major
proteolytic
that
plays
an
important
role
in
the
regulation
of
various
cell
processes,
such
as
cycle,
stress
response,
and
transcriptional
regulation,
especially
neurons,
dysfunction
UPS
considered
to
be
cause
neuronal
death
neurodegenerative
diseases.
However,
mechanism
caused
by
has
not
yet
been
fully
elucidated.
In
this
study,
we
investigated
induced
proteasome
inhibitors
using
human
neuroblastoma
SH-SY5Y
cells.
Z-Leu-D-Leu-Leu-al
(MG132),
inhibitor,
apoptosis
cells
concentration-
time-dependent
manner.
Antioxidants
N-acetylcysteine
EUK-8
attenuated
MG132-induced
apoptosis.
Apocynin
diphenyleneiodonium,
NADPH
oxidase
(NOX),
enzyme
produces
superoxide
anions,
also
It
was
found
MG132
treatment
increased
expression
NOX5,
NOX
family
member,
siRNA-mediated
silencing
NOX5
BAPTA-AM,
which
inhibits
chelating
calcium,
suppressed
production
reactive
oxygen
species
These
results
suggest
induces
through
anion
NOX5.
Journal of Neuroinflammation,
Journal Year:
2023,
Volume and Issue:
20(1)
Published: March 19, 2023
Abstract
Alzheimer’s
disease
(AD)
is
a
chronic
neurodegenerative
disease,
with
the
characteristics
of
neurofibrillary
tangle
(NFT)
and
senile
plaque
(SP)
formation.
Although
great
progresses
have
been
made
in
clinical
trials
based
on
relevant
hypotheses,
these
studies
are
also
accompanied
by
emergence
toxic
side
effects,
it
an
urgent
task
to
explore
underlying
mechanisms
for
benefits
prevent
treat
AD.
Herein,
animal
experiments
few
trials,
neuroinflammation
AD
characterized
long-term
activation
pro-inflammatory
microglia
NOD-,
LRR-
pyrin
domain-containing
protein
3
(NLRP3)
inflammasomes.
Damaged
signals
from
periphery
within
brain
continuously
activate
microglia,
thus
resulting
constant
source
inflammatory
responses.
The
response
exacerbates
endoplasmic
reticulum
oxidative
stress
which
triggers
microglia-dependent
immune
responses,
ultimately
leading
occurrence
deterioration
In
this
review,
we
systematically
summarized
sorted
out
that
exercise
ameliorates
directly
indirectly
regulating
central
nervous
system
promoting
hippocampal
neurogenesis
provide
new
direction
exploring
activity
Nature,
Journal Year:
2023,
Volume and Issue:
620(7975), P. 898 - 903
Published: Aug. 2, 2023
Abstract
The
abnormal
assembly
of
TAR
DNA-binding
protein
43
(TDP-43)
in
neuronal
and
glial
cells
characterizes
nearly
all
cases
amyotrophic
lateral
sclerosis
(ALS)
around
half
frontotemporal
lobar
degeneration
(FTLD)
1,2
.
A
causal
role
for
TDP-43
neurodegeneration
is
evidenced
by
dominantly
inherited
missense
mutations
TARDBP
,
the
gene
encoding
TDP-43,
that
promote
give
rise
to
ALS
FTLD
3–7
At
least
four
types
(A–D)
with
pathology
(FTLD-TDP)
are
defined
distinct
brain
distributions
assembled
associated
different
clinical
presentations
dementia
8
We
previously
showed,
using
cryo-electron
microscopy,
assembles
into
amyloid
filaments
type
B
FTLD-TDP
9
However,
structures
without
remained
unknown.
Here
we
report
microscopy
from
brains
three
individuals
most
common
FTLD-TDP,
A.
formed
a
new
fold
was
same
across
individuals,
indicating
this
may
characterize
FTLD-TDP.
resembles
chevron
badge
unlike
double-spiral-shaped
establishing
filament
folds
neurodegenerative
conditions.
structures,
combination
mass
spectrometry,
led
identification
two
post-translational
modifications
citrullination
monomethylation
R293,
indicate
they
facilitate
formation
observed
structural
variation
individual
filaments.
will
guide
mechanistic
studies
assembly,
as
well
development
diagnostic
therapeutic
compounds
proteinopathies.
Nature Chemical Biology,
Journal Year:
2023,
Volume and Issue:
19(5), P. 607 - 613
Published: Jan. 16, 2023
Abstract
Recent
cryogenic
electron
microscopy
(cryo-EM)
studies
of
infectious,
ex
vivo,
prion
fibrils
from
hamster
263K
and
mouse
RML
strains
revealed
a
similar,
parallel
in-register
intermolecular
β-sheet
(PIRIBS)
amyloid
architecture.
Rungs
the
are
composed
individual
protein
(PrP)
monomers
that
fold
to
create
distinct
N-terminal
C-terminal
lobes.
However,
disparity
in
hamster/mouse
PrP
sequence
precludes
understanding
how
divergent
emerge
an
identical
substrate.
In
this
study,
we
determined
near-atomic
resolution
cryo-EM
structure
vivo
ME7
strain
compared
with
fibril
structure.
This
structural
comparison
two
biologically
mouse-adapted
suggests
defined
folding
subdomains
rungs
way
which
they
interrelated,
providing
definition
intra-species
strain-specific
conformations.
Current Issues in Molecular Biology,
Journal Year:
2024,
Volume and Issue:
46(1), P. 621 - 633
Published: Jan. 9, 2024
In
this
study,
we
review
the
properties
of
three
anionic
detergents,
sodium
dodecyl
sulfate
(SDS),
Sarkosyl,
and
lauroylglutamate
(SLG),
as
they
play
a
critical
role
in
molecular
biology
research.
SDS
is
widely
used
electrophoresis
cell
lysis
for
proteomics.
Sarkosyl
and,
more
frequently,
are
characterization
neuropathological
protein
fibrils
solubilization
proteins.
Many
amyloid
resistant
to
or
different
degrees
thus,
can
be
readily
isolated
from
detergent-sensitive
SLG
milder
than
above
two
detergents
has
been
refolding
proteins
inclusion
bodies.
Here,
show
that
both
have
refolding,
effects
on
native
structure
weaker
SLG,
dissociates
We
propose
may
effective
functional
proteomics
due
no
binding
