In
the
present
thesis,
we
used
a
rodent
analogous
coronavirus,
murine
hepatitis
virus
(MHV),
in
culture
to
directly
assess
its
impact
on
astrocytic
and
microglial
cells.
Given
increasing
importance
of
brain
neurotrophic
factor
(BDNF)-TrkB
signaling
system
glial
functioning,
also
assessed
whether
unique
TrkB.T1
truncated
isoform
(the
only
BDNF
receptor
astrocytes)
would
modulate
reactivity
MHV
viral
infection.
Our
results
largely
support
notion
that
readily
infects
astrocytes
caused
degree
toxicity
these
The
addition
microglia
modulated
magnitude
this
effect
greatly
increased
pro-inflammatory
cytokine
release.
Furthermore,
deficiency
appeared
reduce
astrocyte
viability
morphology.
These
data
may
have
useful
implications
for
better
understanding
nature
responses
coronaviral
infection
TrkB
such
responses.
Cell Death Discovery,
Год журнала:
2024,
Номер
10(1)
Опубликована: Март 19, 2024
Abstract
A
rising
number
of
patient
cases
point
to
a
probable
link
between
SARS-CoV-2
infection
and
Parkinson’s
disease
(PD),
yet
the
mechanisms
by
which
affects
brain
generates
neuropsychiatric
symptoms
in
COVID-19
patients
remain
unknown.
Ferroptosis,
distinct
iron-dependent
non-apoptotic
type
cell
death
characterized
lipid
peroxidation
glutathione
depletion,
key
factor
neurological
disorders.
Ferroptosis
may
have
pathogenic
role
COVID-19,
according
recent
findings,
however
its
potential
contributions
COVID-19-related
PD
not
been
investigated.
This
review
covers
paths
for
brain.
Among
these
putative
processes,
ferroptosis
contribute
etiology
COVID-19-associated
PD,
potentially
providing
therapeutic
methods.
Biological Chemistry,
Год журнала:
2024,
Номер
405(9-10), С. 615 - 625
Опубликована: Авг. 1, 2024
Abstract
In
humans,
up
to
1,500
mitochondrial
precursor
proteins
are
synthesized
at
cytosolic
ribosomes
and
must
be
imported
into
the
organelle.
This
is
not
only
essential
for
but
also
many
functions.
The
majority
of
over
translocase
outer
membrane
(TOM).
recent
years,
high-resolution
structure
analyses
from
different
organisms
shed
light
on
composition
arrangement
TOM
complex.
Although
significant
similarities
have
been
found,
differences
were
observed,
which
favored
during
evolution
could
reflect
manifold
functions
with
cellular
signaling
its
response
altered
metabolic
situations.
A
key
component
within
these
regulatory
mechanisms
TOMM70,
involved
in
protein
import,
forms
contacts
ER
nucleus,
defense
infections.
Biomedicines,
Год журнала:
2024,
Номер
12(10), С. 2257 - 2257
Опубликована: Окт. 4, 2024
Introduction:
Atypical
parkinsonisms
(APs)
present
various
symptoms
including
motor
impairment,
cognitive
decline,
and
autonomic
dysfunction.
Olfactory
loss
(OL),
being
a
significant
non-motor
symptom,
has
emerged
as
an
under-evaluated,
yet
potentially
valuable,
feature
that
might
aid
in
the
differential
diagnosis
of
APs.
State
art:
The
most
pronounced
OL
is
usually
associated
with
Dementia
Lewy
Bodies
(DLB).
While
view
about
normosmic
course
Multiple
System
Atrophy
(MSA)
remains
unchanged,
research
indicates
mild
may
occur
subset
patients
Progressive
Supranuclear
Palsy
(PSP)
Corticobasal
Degeneration
(CBD).
This
be
linked
to
deposition
abnormal
protein
aggregates
central
nervous
system.
Clinical
significance:
aim
this
review
discuss
role
its
degree
pattern
pathogenesis
testing
could
serve
non-invasive,
quick
screening
tool
differentiate
between
APs
project
disease
progression.
Future
directions:
There
need
for
further
evaluation
topic.
lead
development
standardized
olfactory
protocols
implemented
clinical
practice,
making
more
convenient.
Understanding
differences
sense
smell
create
avenue
targeted
therapeutic
strategies.
European Archives of Psychiatry and Clinical Neuroscience,
Год журнала:
2024,
Номер
274(8), С. 1797 - 1817
Опубликована: Ноя. 15, 2024
The
SARS-CoV-2
pandemic
has
resulted
in
762
million
infections
worldwide
from
2020
to
date,
of
which
approximately
ten
percent
are
suffering
the
effects
after
infection
2019
(COVID-19)
[1,
40].
In
Germany,
it
is
now
assumed
that
at
least
one
people
suffer
post-COVID
condition
with
long-term
consequences.
These
have
been
previously
reported
diseases
like
Myalgic
Encephalomyelitis
(ME)
and
Chronic
Fatigue
Syndrome
(CFS).
Symptoms
show
a
changing
variability
recent
surveys
COVID
context
indicate
10-30
%
outpatients,
50
70%
hospitalised
patients
sequelae.
Recent
data
suggest
only
13%
all
ill
were
completely
free
symptoms
recovery
[3,
9].
Current
hypotheses
consider
chronic
inflammation,
mitochondrial
dysfunction,
latent
viral
persistence,
autoimmunity,
changes
human
microbiome
or
multilocular
sequelae
various
organ
system
infection.
Hyperbaric
oxygen
therapy
(HBOT)
applied
since
1957
for
heart
surgery,
scuba
dive
accidents,
CO
intoxication,
air
embolisms
anaerobic
pathogens.
Under
hyperbaric
pressure,
physically
dissolved
blood
higher
concentrations
reaches
levels
four
times
than
under
normobaric
application.
Moreover,
alternation
hyperoxia
normoxia
induces
variety
processes
cellular
level,
improves
supply
areas
locoregional
hypoxia.
Numerous
target
gene
on
new
vessel
formation,
anti-inflammatory
anti-oedematous
demonstrated
[74].
provision
intermittently
high,
local
increases
repair
regeneration
normalises
predominance
hyperinflammation.
At
present
time
prospective,
randomized
placebo-controlled
study
exists
positive
global
cognitive
function,
attention
executive
psychiatric
pain
interference.
conclusion,
up
this
date
HBO
scientifically
proven
treatment
prospective
controlled
trial
be
effective
improvement,
brain
network
improvement
cardiac
function.
HBOT
may
not
theoretical
but
also
potential
impact
targets
current
pathophysiology
Post
condition,
warrants
further
scientific
studies
patients.
Molecular Metabolism,
Год журнала:
2024,
Номер
91, С. 102077 - 102077
Опубликована: Ноя. 30, 2024
Inorganic
polyphosphate
(polyP)
is
an
evolutionary
and
ancient
polymer
composed
by
orthophosphate
units
linked
phosphoanhydride
bonds.
In
mammalian
cells,
polyP
shows
a
high
localization
in
mitochondria,
its
regulatory
role
various
aspects
of
bioenergetics
has
already
been
demonstrated,
via
molecular
mechanism(s)
yet
to
be
fully
elucidated.
recent
years,
for
signal
transduction,
from
brain
physiology
the
bloodstream,
also
emerged.
this
manuscript,
we
explored
intriguing
possibility
that
effects
on
transduction
could
mechanistically
those
exerted
bioenergetics.
To
conduct
our
studies,
used
combination
cellular
animal
models.
Our
findings
demonstrate
first
time
intimate
crosstalk
between
levels
activation
status
AMPK
signaling
pathway,
mechanism
involving
free
phosphate
homeostasis.
key
player
cell
signaling,
crucial
regulator
mitochondrial
results
show
depletion
cells
downregulates
activity
AMPK.
Moreover,
increased
activate
Accordingly,
genetic
downregulation
AMPKF0611
impairs
both
SH-SY5Y
brains
female
mice.
This
manuscript
sheds
new
light
regulation
positions
as
potent
beyond
mere
bioenergetics,
paving
road
using
metabolism
innovative
pharmacological
target
pathologies
characterized
dysregulated
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Фев. 24, 2024
Abstract
Drosophila
Melanogaster
is
widely
used
as
animal
models
for
Parkinson’s
disease
(PD)
research.
Because
of
the
complexity
MoCap
and
quantitative
assessment
among
,
however,
there
a
technical
issue
that
identify
PD
symptoms
within
drosophila
based
on
objective
spontaneous
behavioral
characteristics.
Here,
we
developed
deep
learning
framework
generated
from
kinematic
features
body
posture
motion
between
wildtype
SNCA
E46K
mutant
genetically
modeled
□-Syn,
supporting
clustering
classification
individuals.
We
record
locomotor
activity
in
3D-printed
trap,
utilize
pre-analysis
pose
estimation
software
DeepLabCut
(DLC)
to
calculate
generate
numerical
data
representing
speed,
tremor
frequency,
limb
.
By
plugging
these
input,
diagnosis
result
(1/0)
or
WT
output.
Our
provides
toolbox
which
would
be
valuable
investigation
progressing
pharmacotherapeutic
drug
development.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Июнь 3, 2024
Abstract
Viral
accessory
proteins
play
critical
roles
in
viral
escape
form
host
innate
immune
responses
and
inflammatory
pathogenesis.
Here
we
show
that
the
SARS-CoV-2
protein,
ORF9b,
but
not
other
(ORF3a,
ORF3b,
ORF6,
ORF7,
ORF8,
ORF9c,
ORF10),
strongly
activates
inflammasome-dependent
caspase-1
A549
lung
carcinoma
cells
THP-1
monocyte-macrophage
cells.
Exposure
to
lipopolysaccharide
(LPS)
ATP
additively
enhanced
activation
of
by
suggesting
ORF9b
LPS
follow
parallel
pathways
inflammasome
caspase-1.
Following
rational
silico
approaches,
have
designed
small
molecules
capable
inhibiting
homodimerization
which
experimentally
inhibited
ORF9b-ORF9b
homotypic
interactions,
caused
mitochondrial
eviction
ORF9b-induced
cells,
cytokine
release
restored
type
I
interferon
(IFN-I)
signaling
suppressed
both
cell
models.
These
are
first-in-class
compounds
targeting
a
protein
for
viral-induced
exacerbated
inflammation
from
responses,
with
potential
mitigating
severe
immunopathogenic
damage
induced
highly
pathogenic
coronaviruses
restoring
antiviral
curtailed
infection.
In
the
present
thesis,
we
used
a
rodent
analogous
coronavirus,
murine
hepatitis
virus
(MHV),
in
culture
to
directly
assess
its
impact
on
astrocytic
and
microglial
cells.
Given
increasing
importance
of
brain
neurotrophic
factor
(BDNF)-TrkB
signaling
system
glial
functioning,
also
assessed
whether
unique
TrkB.T1
truncated
isoform
(the
only
BDNF
receptor
astrocytes)
would
modulate
reactivity
MHV
viral
infection.
Our
results
largely
support
notion
that
readily
infects
astrocytes
caused
degree
toxicity
these
The
addition
microglia
modulated
magnitude
this
effect
greatly
increased
pro-inflammatory
cytokine
release.
Furthermore,
deficiency
appeared
reduce
astrocyte
viability
morphology.
These
data
may
have
useful
implications
for
better
understanding
nature
responses
coronaviral
infection
TrkB
such
responses.
