Melatonin regulation of phase separation in Neuro-PASC: out-maneuvering Janus-faced amyloids
Exploration of neuroscience,
Год журнала:
2025,
Номер
4
Опубликована: Март 24, 2025
The
SAR-CoV-2
virus
has
evolved
to
co-exist
with
human
hosts,
albeit
at
a
substantial
energetic
cost
resulting
in
post-infection
neurological
manifestations
[Neuro-post-acute
sequelae
of
SARS-CoV-2
infection
(PASC)]
that
significantly
impact
public
health
and
economic
productivity
on
global
scale.
One
the
main
molecular
mechanisms
responsible
for
development
Neuro-PASC,
individuals
all
ages,
is
formation
inadequate
proteolysis/clearance
phase-separated
amyloid
crystalline
aggregates—a
hallmark
feature
aging-related
neurodegenerative
disorders.
Amyloidogenesis
during
viral
persistence
natural,
inevitable,
protective
defense
response
exacerbated
by
SARS-CoV-2.
Acting
as
chemical
catalyst,
accelerates
hydrophobic
collapse
heterogeneous
nucleation
amorphous
amyloids
into
stable
β-sheet
aggregates.
clearance
aggregates
most
effective
slow
wave
sleep,
when
high
levels
adenosine
triphosphate
(ATP)—a
biphasic
modulator
biomolecular
condensates—and
melatonin
are
available
solubilize
removal.
dysregulation
mitochondrial
dynamics
SARS-CoV-2,
particular
fusion
fission
homeostasis,
impairs
proper
distinct
subpopulations
can
remedy
challenges
created
diversion
substrates
away
from
oxidative
phosphorylation
towards
glycolysis
support
replication
maintenance.
subsequent
reduction
ATP
inhibition
synthesis
sleep
results
incomplete
brain
aggregates,
leading
commonly
associated
age-related
Exogenous
not
only
prevents
dysfunction
but
also
elevates
production,
effectively
augmenting
solubilizing
effect
moiety
ensure
timely,
optimal
disaggregation
pathogenic
prevention
attenuation
Neuro-PASC.
Язык: Английский
Metabolic modelling reveals key pathways in COVID-19 in an effort to drive drug purposing
IFAC-PapersOnLine,
Год журнала:
2024,
Номер
58(23), С. 91 - 96
Опубликована: Янв. 1, 2024
Язык: Английский
Dynamic metabolic modeling of ATP allocation during viral infection
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 13, 2024
Viral
pathogens,
like
SARS-CoV-2,
hijack
the
host's
macromolecular
production
machinery,
imposing
an
energetic
burden
that
is
distributed
across
cellular
metabolism.
To
explore
dynamic
metabolic
tension
between
survival
and
viral
replication,
we
developed
a
computational
framework
uses
genome-scale
models
to
perform
Flux
Balance
Analysis
of
human
cell
metabolism
during
virus
infections.
Relative
previous
models,
our
addresses
physiology
infections
non-proliferating
host
cells
through
two
new
features.
First,
by
incorporating
lipid
content
SARS-CoV-2
biomass,
discovered
activation
previously
overlooked
pathways
giving
rise
predictions
possible
drug
targets.
Furthermore,
introduce
model
simulates
partitioning
resources
cell,
capturing
extent
which
competition
depletes
from
essential
ATP.
By
dynamics
into
COMETS
for
spatio-temporal
modeling
metabolism,
provide
mechanistic,
generalizable
starting
point
bridging
systems
biology
with
pathogenesis.
This
could
be
extended
broadly
incorporate
phage
in
microbial
ecosystems.
Язык: Английский