Nalidixic acid inhibits the aggregation of HSA: Utilizing the molecular simulations to uncover the detailed insights
Computational Biology and Chemistry,
Год журнала:
2025,
Номер
117, С. 108415 - 108415
Опубликована: Фев. 28, 2025
Язык: Английский
Multivalent interaction induces phase separation and formation of more toxic aggregates of α-syn in a yeast model of Parkinson’s disease
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 18, 2025
Abstract
The
process
of
protein
phase
separation,
particularly
in
the
context
intrinsically
disordered
proteins,
has
been
extensively
studied
for
its
implications
several
neuro-degenerative
diseases.
Although
mechanism
separation
and
involved
molecular
grammar
have
well
explored
under
vitro
conditions,
focus
is
now
shifting
towards
developing
more
complex
models
order
to
mimic
biological
systems
closely.
Here,
we
alpha
synuclein
(α-syn),
an
whose
aggregation
implicated
pathology
Parkinson’s
Disease,
(PD)
inside
yeast
cells
(
Saccharomyces
cerevisiae
).
Using
a
positively
charged
polymer;
polyethylenimine
(PEI),
which
binds
presumably
at
negatively
C-terminal
domain
α-syn,
find
that
α-syn
can
be
modulated
by
least
two
pathways:
one
involving
second
without
separation.
We
further
these
pathways
lead
varying
fibril
characteristics
toxicities.
believe
this
model
used
as
quick
convenient
system
screen
novel
repurposed
small
molecules
against
toxic
droplets.
Язык: Английский
Liquid–liquid phase separation and conformational strains of α-Synuclein: implications for Parkinson’s disease pathogenesis
Frontiers in Molecular Neuroscience,
Год журнала:
2024,
Номер
17
Опубликована: Окт. 23, 2024
Parkinson’s
disease
(PD)
and
other
synucleinopathies
are
characterized
by
the
aggregation
deposition
of
alpha-synuclein
(
α
-syn)
in
brain
cells,
forming
insoluble
inclusions
such
as
Lewy
bodies
(LBs)
neurites
(LNs).
The
-syn
is
a
complex
process
involving
structural
conversion
from
its
native
random
coil
to
well-defined
secondary
structures
rich
β
-sheets,
amyloid-like
fibrils.
Evidence
suggests
that
intermediate
species
aggregates
formed
during
this
responsible
for
cell
death.
However,
molecular
events
involved
relationship
with
onset
progression
remain
not
fully
elucidated.
Additionally,
clinical
pathological
heterogeneity
observed
various
has
been
highlighted.
Liquid–liquid
phase
separation
(LLPS)
condensate
formation
have
proposed
alternative
mechanisms
could
underpin
pathology
contribute
seen
synucleinopathies.
This
review
focuses
on
role
cellular
environment
conformational
rearrangement,
which
may
lead
existence
different
strains
varying
toxicity
patterns.
discussion
will
include
stress,
abnormal
LLPS
formation,
potential
pathology.
Язык: Английский
Investigation of new non-toxic inhibitors of fibril formation and preservatives for insulin preparations its analogues
Advances in protein chemistry and structural biology,
Год журнала:
2024,
Номер
unknown
Опубликована: Янв. 1, 2024
Язык: Английский
Proteins Associated with Neurodegenerative Diseases: Link to DNA Repair
Biomedicines,
Год журнала:
2024,
Номер
12(12), С. 2808 - 2808
Опубликована: Дек. 11, 2024
The
nervous
system
is
susceptible
to
DNA
damage
and
repair
defects,
if
not
repaired,
neuronal
cells
can
die,
causing
neurodegenerative
diseases
in
humans.
overall
picture
of
what
known
about
mechanisms
the
still
unclear.
current
challenge
use
accumulated
knowledge
basic
science
on
improve
treatment
disorders.
In
this
review,
we
summarize
understanding
function
repair,
particular,
base
excision
double-strand
break
pathways
as
being
most
important
cells.
We
recent
data
proteins
involved
associated
with
diseases,
particular
emphasis
PARP1
ND-associated
proteins,
which
are
have
ability
undergo
liquid–liquid
phase
separation.
Язык: Английский