International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(16), P. 8923 - 8923
Published: Aug. 16, 2024
Ocrelizumab
(OCR)
is
a
humanized
anti-CD20
monoclonal
antibody
approved
for
both
Relapsing
and
Primary
Progressive
forms
of
Multiple
Sclerosis
(MS)
treatment.
OCR
postulated
to
act
via
rapid
B
cell
depletion;
however,
by
analogy
with
other
agents,
additional
effects
can
be
envisaged,
such
as
on
Protein
Kinase
C
(PKC).
Hence,
this
work
aims
explore
novel
potential
mechanisms
action
in
peripheral
blood
mononuclear
cells
from
MS
patients
before
after
12
months
We
first
assessed,
up-stream,
PKCβII
subsequently
explored
two
down-stream
pathways:
hypoxia-inducible
factor
1
alpha
(HIF-1α)/vascular
endothelial
growth
(VEGF),
human
antigen
R
(HuR)/manganese-dependent
superoxide
dismutase
(MnSOD)
heat
shock
proteins
70
(HSP70).
At
baseline,
higher
levels
PKCβII,
HIF-1α,
VEGF
were
found
compared
healthy
controls
(HC);
interestingly,
the
overexpression
inflammatory
cascade
was
counteracted
Conversely,
at
content
HuR,
MnSOD,
HSP70
significantly
lower
HC,
while
administration
induced
up-regulation
these
neuroprotective
pathways.
These
results
enable
us
disclose
dual
positive
OCR:
anti-inflammatory
neuroprotective.
Therefore,
addition
depletion,
effect
molecular
cascades
contribute
counteracting
disease
progression.
Journal of Neuroinflammation,
Journal Year:
2024,
Volume and Issue:
21(1)
Published: Aug. 21, 2024
Tumor
necrosis
factor
(TNF)
is
a
pleiotropic
cytokine
regulating
many
physiological
and
pathological
immune-mediated
processes.
Specifically,
it
has
been
recognized
as
an
essential
pro-inflammatory
implicated
in
multiple
sclerosis
(MS)
pathogenesis
progression.
MS
chronic
disease
of
the
central
nervous
system,
characterized
by
multifocal
acute
inflammatory
demyelination
white
grey
matter,
along
with
neuroaxonal
loss.
A
recent
concept
field
research
disability
resulting
from
Progression
Independent
Relapse
Activity
(PIRA).
PIRA
recognizes
that
accumulation
since
early
phase
can
occur
independently
relapse
activity
overcoming
traditional
dualistic
view
either
relapsing-inflammatory
or
progressive-neurodegenerative
disease.
Several
studies
have
demonstrated
upregulation
TNF
expression
both
active
brain
lesions.
Additionally,
elevated
levels
observed
serum
cerebrospinal
fluid
patients.
appears
to
play
significant
role
maintaining
intrathecal
inflammation,
promoting
axonal
damage
neurodegeneration,
consequently
contributing
progression
accumulation.
In
summary,
this
review
highlights
current
understanding
its
receptors
progression,
specifically
focusing
on
relatively
unexplored
condition.
Further
area
holds
promise
for
potential
therapeutic
interventions
targeting
mitigate
Brain-derived
neurotrophic
factor
(BDNF)
is
a
neurotrophin,
acting
as
signal
and
neuromodulator
in
the
central
nervous
system
(CNS).
BDNF
synthesized
from
its
precursor
proBDNF
within
CNS
peripheral
tissues.
Through
activation
of
NTRK2/TRKB
(neurotrophic
receptor
tyrosine
kinase
2),
promotes
neuronal
survival,
synaptic
plasticity,
growth,
whereas
it
inhibits
microglial
release
pro-inflammatory
cytokines.
dysregulated
different
neurodegenerative
diseases
depressions.
However,
there
major
controversy
concerning
levels
stages
multiple
sclerosis
(MS).
Therefore,
this
review
discusses
potential
role
signaling
MS,
how
modulators
affect
pathogenesis
outcomes
disease.
International Journal of Molecular Sciences,
Journal Year:
2025,
Volume and Issue:
26(3), P. 884 - 884
Published: Jan. 21, 2025
In
multiple
sclerosis
(MS),
there
is
significant
evidence
indicating
that
both
progression
independent
of
relapse
activity
(PIRA)
and
relapse-related
worsening
events
contribute
to
the
accumulation
progressive
disability
from
onset
disease
throughout
its
course.
Understanding
compartmentalized
pathophysiology
MS
would
enhance
comprehension
mechanisms,
overcoming
traditional
distinction
in
phenotypes.
Smoldering
thought
be
maintained
by
a
continuous
interaction
between
parenchymal
chronic
processes
neuroinflammation
neurodegeneration
intrathecal
compartment.
This
review
provides
comprehensive
up-to-date
overview
neuropathological
immunological
related
mechanisms
underlying
PIRA
phenomena
MS,
with
focus
on
studies
investigating
impact
currently
available
therapies
these
complex
mechanisms.
Annals of Clinical and Translational Neurology,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 17, 2025
Abstract
Objective
To
investigate
ethnoracial
disparities
in
gray
matter
(GM)
atrophy,
the
contribution
of
white
lesions
and
consequent
structural
disconnectivity
among
patients
with
multiple
sclerosis
(MS).
Methods
This
retrospective
study
included
297
MS
(pwMS),
98
Hispanic/Latinx
(H‐MS),
82
non‐Hispanic
Black
(B‐MS),
117
White
(W‐MS).
GM
atrophy
was
assessed
using
univariate,
voxel‐based
morphometry,
multivariate
techniques,
source‐based
morphometry.
Structural
secondary
to
evaluated
network
modification
tool.
Mediation
analyses
explored
relationships
between
groups,
lesions,
disconnectivity,
atrophy.
Results
B‐MS
H‐MS
generally
exhibited
greater
compared
W‐MS,
particularly
temporal,
parahippocampal,
precuneus,
cuneus
GM.
differences
were
most
prominent
hippocampal,
cingulate,
deep
regions.
revealed
that
lesion
load
significantly
mediated
group
global
(percent
=
52.4%),
while
some
specific
components,
notably
matter,
insular,
anterior
cingulate
Interpretation
Significant
exist
its
patterns
diverse
patients,
partially
by
disconnectivity.
These
findings
underscore
importance
considering
factors
research
clinical
practice,
potentially
informing
personalized
treatment
strategies
emphasizing
need
for
representation
trials.
