bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 13, 2024
Abstract
Lewy
pathology
due
to
alpha-synuclein
(α-syn)
inclusions
is
one
of
the
major
hallmarks
Parkinson’s
Disease
(PD).
β-Amyloid
(Aβ)
and
phosphorylated-tau,
pathologies
usually
found
in
Alzheimer’s
(AD),
have
also
been
implicated
PD,
with
over
50%
patients
exhibited
co-expression
these
proteins
(co-pathologies).
In
both
AD
PD
postmortem
tissue,
neuroinflammation
–
activation
microglia
resident
macrophages
infiltration
immune
cells
from
periphery,
including
T
monocytes–are
drivers
neurodegeneration.
However,
how
contribute
inflammatory
response
overall
neurodegenerative
disease
phenotype
remains
unknown.
To
understand
drives
neuropathology,
we
developed
a
novel
co-pathology
model
by
stereotaxically
injecting
α-syn
pre-formed
fibrils
(PFFs)
into
striatum,
AAV-double
mut
tau
virus
entorhinal
cortex,
3-month-old
J20
transgenic
mice
Aβ
pathology.
We
analyzed
cell
populations
brain
periphery
at
3
months
post-induction
(3MPI).
At
6MPI,
neuronal
loss
hippocampus
substantia
nigra
pars
compacta
were
assessed
along
pathological
protein
deposition.
3MPI,
mouse
begins
exhibit
enhanced
load
cortex
hippocampus.
There
was
robust
neuroinflammatory
interconnected
regions,
increased
microglial
number,
changes
markers,
cells.
This
synergistic
model,
compared
individual
models,
supporting
hypothesis
that
collectively
may
drive
progression
disease.
ACS Chemical Neuroscience,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 14, 2025
The
dysregulation
of
T
cell
differentiation
was
associated
with
cognitive
impairment.
Recently,
the
peripheric
β-secretase
(BACE1)
has
been
suggested
as
a
regulator
differentiation,
which
increased
in
both
impairment
(CI)
and
type
2
diabetes
mellitus
(T2DM)
CI
patients.
However,
relationship
between
dysfunction
remains
unclear.
To
address
this
question,
we
measured
subtypes
BACE1
enzyme
activity
clinical
cohort
5xFAD
mice.
We
found
that
IFNγ+
Th1
Tc1
cells
were
T2DM-CI
groups,
worsening
function.
elevated
IFNγ
+
also
observed
8-month-old
BACE1-mediated
INSR
cleavage
cells.
These
findings
demonstrate
potential
role
CI.
Frontiers in Immunology,
Journal Year:
2025,
Volume and Issue:
16
Published: April 2, 2025
The
intricate
interaction
between
skeletal
muscle
biomechanics,
the
tumor
microenvironment,
and
immunotherapy
constitutes
a
pivotal
research
focus
oncology.
This
work
provides
comprehensive
review
of
methodologies
for
evaluating
including
handheld
dynamometry,
advanced
imaging
techniques,
electrical
impedance
myography,
elastography,
single-fiber
experiments
to
assess
quality
performance.
Furthermore,
it
elucidates
mechanisms,
applications,
limitations
various
modalities,
immune
checkpoint
inhibitors,
adoptive
cell
therapy,
cancer
vaccines,
combined
chemoimmunotherapy,
while
examining
their
effects
on
function
systemic
responses.
Key
findings
indicate
that
although
is
effective
in
augmenting
antitumor
immunity,
frequently
induces
muscle-related
adverse
such
as
weakness,
fatigue,
or
damage,
primarily
mediated
by
cytokine
release
activation.
underscores
significance
niches
within
microenvironment
influencing
treatment
outcomes
proposes
strategies
optimize
therapy
through
personalized
regimens
combinatorial
approaches.
highlights
need
further
formation
interactions
muscle-tumor.
Our
crucial
advancing
efficacy
immunotherapy,
reducing
effects,
ultimately
improving
survival
rates
life
patients
with
cancer.
Neurobiology of Disease,
Journal Year:
2025,
Volume and Issue:
unknown, P. 106896 - 106896
Published: April 1, 2025
Ischemic
stroke,
responsible
for
80
%
of
all
strokes,
is
a
leading
cause
mortality
globally.
While
altered
lipids
profiles
are
recognized
as
modifiable
risk
factors,
their
direct
impact
on
stroke
outcomes
less
understood
due
to
the
brain's
distinct
lipid
metabolism
and
selective
permeability
blood-brain
barrier
lipoproteins.
As
key
components
lipoproteins,
apolipoproteins
essential
transport,
redistribution
in
both
central
nervous
system
peripheral
blood
circulation.
This
review
provides
an
updated
perspective
influence
brain-expressed
(such
ApoE,
ApoA-I,
ApoJ,
ApoD,
others)
those
that
cross
damaged
following
ischemic
stroke.
We
explore
hypotheses
regarding
involvement
molecular
pathways
related
metabolism,
inflammation,
oxidative
stress,
mitochondrial
function
integrity.
Through
this
synthesis,
we
aim
identify
potential
biomarkers
therapeutic
targets,
thereby
enhancing
our
understanding
progression
contributing
improved
clinical
outcomes.
Journal of Neuroscience Research,
Journal Year:
2024,
Volume and Issue:
102(7)
Published: July 1, 2024
Abstract
Central
and
peripheral
nervous
system
(CNS/PNS)
proteoglycans
(PGs)
have
diverse
functional
roles,
this
study
examined
how
these
control
cellular
behavior
tissue
function.
The
CNS/PNS
extracellular
matrix
(ECM)
is
a
dynamic,
responsive,
highly
interactive,
space‐filling,
cell
supportive,
stabilizing
structure
maintaining
compartments,
ionic
microenvironments,
microgradients
that
regulate
neuronal
activity
maintain
the
neuron
in
an
optimal
microenvironment.
contains
high
glycosaminoglycan
content
(60%
hyaluronan,
HA)
range
of
PGs.
Immobilization
HA
brain
tissues
by
interactive
hyalectan
PGs
preserves
hydration
activity,
paucity
results
pro‐convulsant
epileptic
phenotype.
Diverse
CS,
KS,
HSPGs
stabilize
blood–brain
barrier
neurovascular
unit,
provide
smart
gel
neurotransmitter
vesicle
storage
delivery,
organize
neuromuscular
junction
basement
membrane,
motor
synaptic
plasticity,
photoreceptor
functions.
PG‐HA
networks
fluxes
compartments
contribute
to
membrane
polarization
dynamics
essential
activation
neurotransduction.
Hyalectans
form
neuroprotective
perineuronal
nets
contributing
memory,
cognitive
learning.
Sialoglycoprotein
associated
with
cones
rods
(SPACRCAN),
binding
CSPG,
stabilizes
inter‐photoreceptor
ECM.
pikachurin
eyes
shut
synapse
aiding
phototransduction
neurotransduction
retinal
bipolar
neurons
crucial
visual
acuity.
This
achieved
through
Laminin
G
motifs
pikachurin,
shut,
neurexins
interact
dystroglycan–cytoskeleton–ECM‐stabilizing
interconnections,
specificity,
co‐ordination
regulatory
action
potentials
neural
networks.
