The Journal of Physical Chemistry B,
Journal Year:
2024,
Volume and Issue:
128(44), P. 10870 - 10879
Published: Oct. 26, 2024
Protein
aggregation
resulting
in
either
ordered
amyloids
or
amorphous
aggregates
is
not
only
restricted
to
deadly
human
diseases
but
also
associated
with
biotechnological
challenges
encountered
the
therapeutic
and
food
industries.
Elucidating
key
structural
determinants
of
protein
important
devise
targeted
inhibitory
strategies,
it
still
remains
a
formidable
task
owing
underlying
hierarchy,
stochasticity,
complexity
self-assembly
processes.
Additionally,
alterations
solution
pH,
salt
types,
ionic
strength
modulate
various
noncovalent
interactions,
thus
affecting
propensity
kinetics.
However,
molecular
origin
detailed
understanding
effects
weakly
strongly
hydrated
salts
on
their
plausible
roles
dissolution
remain
elusive.
In
this
study,
using
fluorescence
circular
dichroism
spectroscopy
combination
electron
microscopy
light
scattering
techniques,
we
show
that
size,
valency,
extent
hydration
cations
play
crucial
role
regulating
disaggregation
processes,
which
may
elicit
unique
methods
for
governing
balance
between
disassembly.
Journal of the American Chemical Society,
Journal Year:
2024,
Volume and Issue:
146(12), P. 8394 - 8406
Published: March 13, 2024
Aggregation
refers
to
the
assembly
of
proteins
into
nonphysiological
higher
order
structures.
While
amyloid
has
been
studied
extensively,
much
less
is
known
about
amorphous
aggregation,
a
process
that
interferes
with
protein
expression
and
storage.
Free
arginine
(Arg+)
widely
used
aggregation
inhibitor,
but
its
mechanism
remains
elusive.
Focusing
on
myoglobin
(Mb),
we
recently
applied
atomistic
molecular
dynamics
(MD)
simulations
for
gaining
detailed
insights
(Ng
J.
Phys.
Chem.
B
2021,
125,
13099).
Building
approach,
current
work
first
time
demonstrates
MD
can
directly
elucidate
inhibition
mechanisms.
Comparative
without
Arg+
reproduced
experimental
finding
significantly
decreased
Mb
propensity.
Our
data
reveal
that,
Arg+,
protein–protein
encounter
complexes
readily
form
salt
bridges
hydrophobic
contacts,
culminating
in
firmly
linked
dimeric
nuclei.
promotes
dissociation
complexes.
These
"unproductive"
are
favored
because
binding
D–
E–
lowers
tendency
these
anionic
residues
interprotein
bridges.
Side
chain
blockage
mediated
largely
by
guanidinium
group
which
binds
carboxylates
through
H-bond-reinforced
ionic
contacts.
revealed
self-association
dynamic
quasi-infinite
network,
found
no
evidence
this
important
inhibition.
Instead,
similar
free
ions.
The
computational
strategy
here
should
be
suitable
rational
design
inhibitors
enhanced
potency.
International Journal of Molecular Sciences,
Journal Year:
2025,
Volume and Issue:
26(2), P. 844 - 844
Published: Jan. 20, 2025
Oxidative
stress
(OS),
generated
by
the
overrun
of
reactive
species
oxygen
and
nitrogen
(RONS),
is
key
cause
several
human
diseases.
With
inflammation,
OS
responsible
for
onset
development
clinical
signs
pathological
hallmarks
Alzheimer’s
disease
(AD).
AD
a
multifactorial
chronic
neurodegenerative
syndrome
indicated
form
progressive
dementia
associated
with
aging.
While
one-target
drugs
only
soften
its
symptoms
while
generating
drug
resistance,
multi-target
polyphenols
from
fruits
vegetables,
such
as
ellagitannins
(ETs),
ellagic
acid
(EA),
urolithins
(UROs),
having
potent
antioxidant
radical
scavenging
effects
capable
counteracting
OS,
could
be
new
green
options
to
treat
degenerative
diseases,
thus
representing
hopeful
alternatives
and/or
adjuvants
ameliorate
AD.
Unfortunately,
in
vivo
ETs
are
not
absorbed,
providing
mainly
which,
due
trivial
water-solubility
first-pass
effect,
metabolizes
intestine
yield
UROs,
or
irreversible
binding
cellular
DNA
proteins,
which
have
very
low
bioavailability,
failing
therapeutic
vivo.
Currently,
UROs
confirmed
beneficial
effect
demonstrated
vitro
reaching
tissues
extent
necessary
outcomes.
upon
administration
food
rich
EA,
URO
formation
affected
extreme
interindividual
variability
that
renders
them
unreliable
novel
clinically
usable
drugs.
Significant
attention
has
therefore
been
paid
specifically
multitarget
incessantly
investigated
nanotechnologically
manipulated
potential
“lead
compound”
protective
action
toward
An
overview
multi-factorial
aspects
characterize
polyphenol
activity,
respectively,
well
traditional
innovative
treatments
available
AD,
constitutes
opening
this
work.
Upon
focus
on
pathophysiology
EA’s
chemical
features
mechanisms
leading
an
all-around
updated
analysis
current
EA-rich
foods
EA
involvement
field
provided.
The
possible
usage
discussed,
reporting
results
applications
vitro,
vivo,
during
trials.
A
critical
view
need
more
extensive
use
most
rapid
diagnostic
methods
detect
early
also
included
