Neural Excitatory/Inhibitory Imbalance in Motor Aging: From Genetic Mechanisms to Therapeutic Challenges
Biology,
Год журнала:
2025,
Номер
14(3), С. 272 - 272
Опубликована: Март 7, 2025
Neural
excitatory/inhibitory
(E/I)
imbalance
plays
a
pivotal
role
in
the
aging
process.
However,
despite
its
significant
impact,
of
E/I
motor
dysfunction
and
neurodegenerative
diseases
has
not
received
sufficient
attention.
This
review
explores
mechanisms
underlying
through
lens
balance,
emphasizing
genetic
molecular
factors
that
contribute
to
this
(such
as
SCN2A,
CACNA1C,
GABRB3,
GRIN2A,
SYT,
BDNF…).
Key
regulatory
genes,
including
REST,
vps-34,
STXBP1,
are
examined
for
their
roles
modulating
synaptic
activity
neuronal
function
during
aging.
With
insights
drawn
from
ALS,
we
discuss
how
disruptions
balance
pathophysiology
age-related
dysfunction.
The
genes
discussed
above
exhibit
certain
association
with
neuron
(like
ALS),
relationship
had
been
previously
recognized.
Innovative
therapies,
such
gene
editing
technology
optogenetic
manipulation,
emerging
promising
tools
restoring
offering
hope
ameliorating
deficits
potential
these
technologies
intervene
aging-related
diseases,
challenges
direct
application
human
conditions.
Язык: Английский
Pathophysiology, Clinical Heterogeneity, and Therapeutic Advances in Amyotrophic Lateral Sclerosis: A Comprehensive Review of Molecular Mechanisms, Diagnostic Challenges, and Multidisciplinary Management Strategies
Life,
Год журнала:
2025,
Номер
15(4), С. 647 - 647
Опубликована: Апрель 14, 2025
Amyotrophic
lateral
sclerosis
(ALS)
is
a
progressive
neurodegenerative
disorder
characterized
by
the
degeneration
of
upper
and
lower
motor
neurons,
leading
to
muscle
atrophy,
paralysis,
respiratory
failure.
This
comprehensive
review
synthesizes
current
knowledge
on
ALS
pathophysiology,
clinical
heterogeneity,
diagnostic
frameworks,
evolving
therapeutic
strategies.
Mechanistically,
arises
from
complex
interactions
between
genetic
mutations
(e.g.,
in
C9orf72,
SOD1,
TARDBP
(TDP-43),
FUS)
dysregulated
cellular
pathways,
including
impaired
RNA
metabolism,
protein
misfolding,
nucleocytoplasmic
transport
defects,
prion-like
propagation
toxic
aggregates.
Phenotypic
manifesting
as
bulbar-,
spinal-,
or
respiratory-onset
variants,
complicates
its
early
diagnosis,
which
thus
necessitates
rigorous
application
revised
El
Escorial
criteria
emerging
biomarkers
such
neurofilament
light
chain.
Clinically,
intersects
with
frontotemporal
dementia
(FTD)
up
50%
cases,
driven
shared
TDP-43
pathology
C9orf72
hexanucleotide
expansions.
Epidemiological
studies
have
revealed
lifetime
risk
1:350,
male
predominance
(1.5:1)
peak
onset
50
70
years.
Disease
progression
varies
widely,
median
survival
2–4
years
post-diagnosis,
underscoring
urgency
for
intervention.
Approved
therapies,
riluzole
(glutamate
modulation),
edaravone
(antioxidant),
tofersen
(antisense
oligonucleotide),
offer
modest
benefits,
while
dextromethorphan/quinidine
alleviates
pseudobulbar
affect.
Non-pharmacological
treatment
advances,
non-invasive
ventilation
(NIV),
prolong
13
months
improve
quality
life,
particularly
bulb-involved
patients.
Multidisciplinary
care—integrating
physical
therapy,
support,
nutritional
management,
cognitive
assessments—is
critical
addressing
non-motor
symptoms
dysphagia,
spasticity,
sleep
disturbances).
Emerging
therapies
show
promise
preclinical
models.
However,
challenges
persist
translating
insights
into
universally
effective
treatments.
Ethical
considerations,
euthanasia
end-of-life
decision-making,
further
highlight
need
patient-centered
communication
palliative
Язык: Английский
Genetic architecture of amyotrophic lateral sclerosis: a comprehensive review
Journal of genetics and genomics/Journal of Genetics and Genomics,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 1, 2025
Язык: Английский
Dynamics of Onset and Progression in Amyotrophic Lateral Sclerosis
Brain Sciences,
Год журнала:
2025,
Номер
15(6), С. 601 - 601
Опубликована: Июнь 3, 2025
This
review
focuses
on
the
complexities
of
amyotrophic
lateral
sclerosis
(ALS)
onset,
highlighting
insidious
nature
disease
and
challenges
in
defining
its
precise
origin
early
pathogenic
mechanisms.
The
clinical
presentation
ALS
is
characterised
by
progressive
muscle
weakness
wasting,
often
with
widespread
fasciculations,
reflecting
lower
motor
neuron
hyperexcitability.
disease’s
pathogenesis
involves
a
prolonged
preclinical
phase
neuronal
proteinopathy,
particularly
TDP-43
accumulation,
which
eventually
leads
to
death
overt
ALS.
discusses
difficulties
detecting
this
transition
implications
for
therapeutic
intervention.
It
also
addresses
involvement
both
upper
systems,
as
well
importance
following
presymptomatic
patients
genetic
mutations.
significance
understanding
distinct
processes
deposition
subsequent
degeneration
developing
effective
treatments
emphasised.
Язык: Английский