Biology,
Journal Year:
2024,
Volume and Issue:
13(9), P. 719 - 719
Published: Sept. 12, 2024
Neurodegenerative
diseases
(NDs),
like
amyotrophic
lateral
sclerosis
(ALS),
Alzheimer's
disease
(AD),
and
Parkinson's
(PD),
primarily
affect
the
central
nervous
system,
leading
to
progressive
neuronal
loss
motor
cognitive
dysfunction.
However,
recent
studies
have
revealed
that
muscle
tissue
also
plays
a
significant
role
in
these
diseases.
ALS
is
characterized
by
severe
wasting
as
result
of
neuron
degeneration,
well
alterations
gene
expression,
protein
aggregation,
oxidative
stress.
Muscle
atrophy
mitochondrial
dysfunction
are
observed
AD,
which
may
exacerbate
decline
due
systemic
metabolic
dysregulation.
PD
patients
exhibit
fiber
atrophy,
altered
composition,
α-synuclein
aggregation
within
cells,
contributing
symptoms
progression.
Systemic
inflammation
impaired
degradation
pathways
common
among
disorders,
highlighting
key
player
Understanding
muscle-related
changes
offers
potential
therapeutic
avenues,
such
targeting
function,
reducing
inflammation,
promoting
regeneration
with
exercise
pharmacological
interventions.
This
review
emphasizes
importance
considering
an
integrative
approach
neurodegenerative
research,
both
peripheral
pathological
mechanisms,
order
develop
more
effective
treatments
improve
patient
outcomes.
Signal Transduction and Targeted Therapy,
Journal Year:
2024,
Volume and Issue:
9(1)
Published: Aug. 23, 2024
Abstract
Alzheimer’s
disease
(AD)
stands
as
the
predominant
form
of
dementia,
presenting
significant
and
escalating
global
challenges.
Its
etiology
is
intricate
diverse,
stemming
from
a
combination
factors
such
aging,
genetics,
environment.
Our
current
understanding
AD
pathologies
involves
various
hypotheses,
cholinergic,
amyloid,
tau
protein,
inflammatory,
oxidative
stress,
metal
ion,
glutamate
excitotoxicity,
microbiota-gut-brain
axis,
abnormal
autophagy.
Nonetheless,
unraveling
interplay
among
these
pathological
aspects
pinpointing
primary
initiators
require
further
elucidation
validation.
In
past
decades,
most
clinical
drugs
have
been
discontinued
due
to
limited
effectiveness
or
adverse
effects.
Presently,
available
primarily
offer
symptomatic
relief
often
accompanied
by
undesirable
side
However,
recent
approvals
aducanumab
(
1
)
lecanemab
2
Food
Drug
Administration
(FDA)
present
potential
in
disrease-modifying
Nevertheless,
long-term
efficacy
safety
need
Consequently,
quest
for
safer
more
effective
persists
formidable
pressing
task.
This
review
discusses
pathogenesis,
advances
diagnostic
biomarkers,
latest
updates
trials,
emerging
technologies
drug
development.
We
highlight
progress
discovery
selective
inhibitors,
dual-target
allosteric
modulators,
covalent
proteolysis-targeting
chimeras
(PROTACs),
protein-protein
interaction
(PPI)
modulators.
goal
provide
insights
into
prospective
development
application
novel
drugs.
Molecular Biomedicine,
Journal Year:
2023,
Volume and Issue:
4(1)
Published: Nov. 8, 2023
Abstract
The
Janus
kinase-signal
transducer
and
transcription
activator
pathway
(JAK-STAT)
serves
as
a
cornerstone
in
cellular
signaling,
regulating
physiological
pathological
processes
such
inflammation
stress.
Dysregulation
this
can
lead
to
severe
immunodeficiencies
malignancies,
its
role
extends
neurotransduction
pro-inflammatory
signaling
mechanisms.
Although
JAK
inhibitors
(Jakinibs)
have
successfully
treated
immunological
inflammatory
disorders,
their
application
has
generally
been
limited
diseases
with
similar
pathogenic
features.
Despite
the
modest
expression
of
JAK-STAT
CNS,
it
is
crucial
for
functions
cortex,
hippocampus,
cerebellum,
making
relevant
conditions
like
Parkinson's
disease
other
neuroinflammatory
disorders.
Furthermore,
influence
on
serotonin
receptors
phospholipase
C
implications
stress
mood
This
review
expands
understanding
JAK-STAT,
moving
beyond
traditional
contexts
explore
stress-related
disorders
CNS
function.
Recent
findings,
effectiveness
Jakinibs
chronic
rheumatoid
arthritis,
expand
therapeutic
applicability.
Advances
isoform-specific
inhibitors,
including
filgotinib
upadacitinib,
promise
greater
specificity
fewer
off-target
effects.
Combination
therapies,
involving
monoclonal
antibodies,
aiming
enhance
efficacy
also
give
great
hope.
Overall,
bridges
gap
between
basic
science
clinical
application,
elucidating
complex
human
health
guiding
future
interventions.
Graphical
Cells,
Journal Year:
2024,
Volume and Issue:
13(6), P. 511 - 511
Published: March 14, 2024
Neuroinflammatory
and
neurodegenerative
disorders
including
Alzheimer’s
disease
(AD),
Parkinson’s
(PD),
traumatic
brain
injury
(TBI)
Amyotrophic
lateral
sclerosis
(ALS)
are
chronic
major
health
disorders.
The
exact
mechanism
of
the
neuroimmune
dysfunctions
these
pathogeneses
is
currently
not
clearly
understood.
These
show
dysregulated
inflammatory
responses,
activation
neurons,
glial
cells,
neurovascular
unit
damage
associated
with
excessive
release
proinflammatory
cytokines,
chemokines,
neurotoxic
mediators,
infiltration
peripheral
immune
cells
into
brain,
as
well
entry
mediators
through
damaged
endothelial
blood–brain
barrier
tight
junction
proteins.
Activation
leads
to
many
molecules
that
cause
neuroinflammation
neurodegeneration.
Gulf
War
Illness
(GWI)
myalgic
encephalomyelitis/chronic
fatigue
syndrome
(ME/CFS)
also
dysfunctions.
Currently,
there
no
effective
disease-modifying
therapeutic
options
available
for
diseases.
Human
induced
pluripotent
stem
cell
(iPSC)-derived
astrocytes,
microglia,
pericytes
used
models
drug
discovery.
This
review
highlights
certain
recent
trends
in
neuroinflammatory
responses
iPSC-derived
applications
Neurobiology of Disease,
Journal Year:
2024,
Volume and Issue:
192, P. 106426 - 106426
Published: Feb. 6, 2024
The
term
"glymphatic"
emerged
roughly
a
decade
ago,
marking
pivotal
point
in
neuroscience
research.
glymphatic
system,
glial-dependent
perivascular
network
distributed
throughout
the
brain,
has
since
become
focal
of
investigation.
There
is
increasing
evidence
suggesting
that
impairment
system
appears
to
be
common
feature
neurodegenerative
disorders,
and
this
exacerbates
as
disease
progression.
Nevertheless,
factors
contributing
dysfunction
across
most
disorders
remain
unclear.
Inflammation,
however,
suspected
play
role.
Dysfunction
can
lead
significant
accumulation
protein
waste
products,
which
trigger
inflammation.
interaction
between
inflammation
cyclical
potentially
synergistic.
Yet,
current
research
limited,
there
lack
comprehensive
models
explaining
association.
In
perspective
review,
we
propose
novel
model
inflammation,
impaired
function,
interconnected
vicious
cycle.
By
presenting
experimental
from
existing
literature,
aim
demonstrate
that:
(1)
aggravates
dysfunction,
(2)
exacerbated
progression,
(3)
progression
promotes
Finally,
implication
proposed
discussed.
