Cell Reports,
Journal Year:
2024,
Volume and Issue:
43(4), P. 114014 - 114014
Published: April 1, 2024
The
transmembrane
channel-like
(TMC)
protein
family
comprises
eight
members,
with
TMC1
and
TMC2
being
extensively
studied.
This
study
demonstrates
substantial
co-expression
of
TMC7
the
mechanosensitive
channel
Piezo2
in
somatosensory
neurons.
Genetic
deletion
primary
sensory
ganglia
neurons
vivo
enhances
sensitivity
both
physiological
pathological
mechanosensory
transduction.
leads
to
an
increase
proportion
rapidly
adapting
(RA)
currents
conducted
by
dorsal
root
ganglion
(DRG)
accelerates
RA
deactivation
kinetics.
In
HEK293
cells
expressing
proteins,
significantly
suppresses
current
amplitudes
co-expressed
Piezo2.
Our
findings
reveal
that
exhibit
physical
interactions,
proteins
also
physically
interact
cytoskeletal
β-actin.
We
hypothesize
functions
as
inhibitory
modulator
DRG
neurons,
either
through
direct
inhibition
or
disrupting
transmission
mechanical
forces
from
cytoskeleton
channel.
International Journal of Molecular Sciences,
Journal Year:
2023,
Volume and Issue:
24(11), P. 9144 - 9144
Published: May 23, 2023
Microglia
are
the
resident
immune
cells
of
central
nervous
system
that
guarantee
surveillance
and
exert
also
a
modulating
role
on
neuronal
synaptic
development
function.
Upon
injury,
microglia
get
activated
modify
their
morphology
acquiring
an
ameboid
phenotype
pro-
or
anti-inflammatory
features.
The
active
in
blood–brain
barrier
(BBB)
function
interaction
with
different
cellular
components
BBB—endothelial
cells,
astrocytes
pericytes—are
described.
Here,
we
report
specific
crosstalk
all
BBB
cell
types
focusing
particular
involvement
modulation
neuroinflammatory
conditions
occur
conjunction
acute
event,
such
as
stroke,
slow
neurodegenerative
disease,
Alzheimer’s
disease.
potential
to
dual
role,
either
protective
detrimental,
depending
disease
stages
environmental
conditioning
factors
is
discussed.
Aggregate,
Journal Year:
2023,
Volume and Issue:
4(4)
Published: March 10, 2023
Abstract
Protein
amyloid
aggregation
has
been
widely
observed
to
occur
and
plays
important
roles
in
both
physiological
processes
pathological
diseases.
Remarkably,
aggregates
assembled
by
native
proteins
gain
a
variety
of
different
biological
activities,
which
cannot
be
adopted
the
unassembled
protein
alone.
Thus,
it
is
investigate
molecular
basis
self‐assembly
how
aggregated
structure
determines
its
function.
In
review,
we
firstly
introduce
our
structural
knowledge
on
undergo
conformational
transition
assemble
into
aggregate,
with
main
focus
fibril,
major
species
aggregate.
Then,
elaborate
structures
fibrils
enable
them
fulfill
highly
diverse
functions
either
or
condition.
Furthermore,
discuss
polymorph
very
unique
feature
implication
understanding
structure‐function
relationship
fibrils.
Finally,
point
out
importance
applying
integrating
new
approaches
for
deepening
study
highlight
potential
designing
fibril‐based
functional
bio‐nanomaterials
application.
European Journal of Medicinal Chemistry,
Journal Year:
2024,
Volume and Issue:
273, P. 116502 - 116502
Published: May 14, 2024
The
cation
channel
Piezo1,
a
crucial
mechanotransducer
found
in
various
organs
and
tissues,
has
gained
considerable
attention
as
therapeutic
target
recent
years.
Following
this
trend,
several
Piezo1
inhibitors
have
been
discovered
studied
for
potential
pharmacological
properties.
This
review
provides
an
overview
of
the
structural
functional
importance
well
discussing
biological
activities
based
on
their
mechanism
action.
compounds
addressed
include
toxin
GsMTx4,
Aβ
peptides,
certain
fatty
acids,
ruthenium
red
gadolinium,
Dooku1,
natural
products
tubeimoside
I,
salvianolic
acid
B,
jatrorrhzine,
escin.
findings
revealed
that
misexpression
can
be
associated
with
number
chronic
diseases,
including
hypertension,
cancer,
hemolytic
anemia.
Consequently,
inhibiting
subsequent
calcium
influx
beneficial
effects
pathological
processes,
shown
by
many
vitro
vivo
studies.
However,
development
is
still
its
beginnings,
opportunities
challenges
remaining
to
explored.
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: July 10, 2024
The
emergence
of
single
nucleus
RNA
sequencing
(snRNA-seq)
offers
to
revolutionize
the
study
Alzheimer's
disease
(AD).
Integration
with
complementary
multiomics
data
such
as
genetics,
proteomics
and
clinical
provides
powerful
opportunities
link
cell
subpopulations
molecular
networks
a
broader
disease-relevant
context.
We
report
snRNA-seq
profiles
from
superior
frontal
gyrus
samples
101
well
characterized
subjects
Banner
Brain
Body
Donation
Program
in
combination
whole
genome
sequences.
findings
that
common
AD
risk
variants
CR1
expression
oligodendrocytes
alterations
hematological
parameters.
observed
an
AD-associated
CD83(+)
microglial
subtype
unique
which
is
associated
immunoglobulin
IgG4
production
transverse
colon.
Our
major
observations
were
replicated
two
additional,
independent
sets.
These
illustrate
power
multi-tissue
profiling
contextualize
brain
transcriptomics
reveal
biology.
Advanced Science,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 14, 2025
α-Syn
fibrils,
a
key
pathological
hallmark
of
Parkinson's
disease,
is
closely
associated
with
disease
initiation
and
progression.
Several
small
molecules
are
found
to
bind
or
dissolve
α-syn
offering
potential
therapeutic
applications.
Here,
an
innovative
optical
tweezers-based,
fluorescence-combined
approach
developed
probe
the
mechanical
characteristics
fibrils
at
single-molecule
level.
When
subjected
axial
stretching,
local
deformation
within
appeared
forces
above
50
pN.
These
structural
alternations
occurred
stepwise
irreversible,
suggesting
unfolding
individual
subdomains.
Additionally,
exhibits
high
heterogeneity
in
lateral
disruption,
rupture
force
ranging
from
500
The
impact
different
compounds
on
structure
features
further
examined.
Notably,
epigallocatechin
gallate
(EGCG)
generally
attenuates
by
wedging
into
N-terminal
polar
groove
induces
fibril
dissociation.
Conversely,
copper
chlorophyllin
A
(CCA)
attaches
four
sites
wrapping
around
core,
reinforcing
stability
against
forces.
work
offers
effective
method
for
characterizing
single-fibril
properties
bridges
compound-induced
response.
insights
valuable
understanding
amyloid
mechanics
their
regulation
molecules.
Molecular Neurobiology,
Journal Year:
2023,
Volume and Issue:
61(5), P. 2808 - 2821
Published: Nov. 8, 2023
Abstract
Extracellular
deposits
of
amyloid-β
(Aβ)
in
the
form
plaques
are
one
main
pathological
hallmarks
Alzheimer’s
disease
(AD).
Over
years,
many
different
Aβ
plaque
morphologies
such
as
neuritic
plaques,
dense
cored
cotton
wool
coarse-grain
and
diffuse
have
been
described
AD
postmortem
brain
tissues,
but
correlation
a
given
type
with
progression
or
symptoms
is
not
clear.
Furthermore,
exact
trigger
causing
development
morphological
subtype
over
other
still
unknown.
Here,
we
review
current
knowledge
about
subset
surrounded
by
swollen
dystrophic
neurites,
which
represent
most
detrimental
consequential
morphology.
Neuritic
associated
local
immune
activation,
neuronal
network
dysfunction,
cognitive
decline.
Given
that
at
interface
deposition,
tau
aggregation,
argue
understanding
mechanism
formation
crucial
to
develop
targeted
therapies
for
AD.
Abstract
Alzheimer's
disease
(AD)
is
the
most
prevailing
form
of
dementia,
with
long‐term
high‐fat
diet
(HFD)
consumption
being
a
pivotal
contributor
to
AD
pathogenesis.
As
microglial
dysfunction
crucial
factor
in
onset,
it
becomes
imperative
explore
effects
HFD
on
function
and
In
present
study,
3xTg‐AD
model
mice
at
age
9‐month
are
subjected
random
allocation,
one
group
receiving
standard
(ND)
other
an
for
3
months.
Subsequently,
transcriptomic
profiling
microglia
unveils
that
alters
fatty
acid
metabolism
mediates
T
cell
infiltration.
Within
hippocampus,
exhibit
aberrant
morphology
lipid
accretion
response
HFD,
evidenced
by
conspicuously
enlarged
bodies
accumulation
droplets.
These
lipid‐droplet‐accumulating
diminished
migratory
capacity
compromise
plaque
consolidation,
thereby
exacerbating
β‐amyloid.
Noteworthy,
induces
infiltration,
aggravating
neuroinflammation
Tau
phosphorylation.
Morris
water
maze
test
reveals
HFD‐consuming
display
marked
impairment
memory
performance.
summary,
this
study
demonstrates
prolonged
exacerbates
amyloid
deposition,
tau
pathology,
cognitive
deficits,
which
associated
droplets
within
microglia.
