Annals of Neurosciences,
Год журнала:
2023,
Номер
30(2), С. 124 - 132
Опубликована: Янв. 13, 2023
Different
studies
identified
the
presence
of
several
altered
genes
in
familial
and
sporadic
amyotrophic
lateral
sclerosis
(ALS)
forms.
The
experimental
data,
together
with
epidemiological
would
seem
to
suggest
existence
molecular
mechanisms
(e.g.,
axonal
transport)
related
these
genes,
a
susceptibility
same
certain
environmental
factors
that
therefore
an
impact
environment
on
etiopathogenesis
ALS.
In
our
review,
we
considered
most
relevant
clusters
around
world,
collecting
different
hypotheses
underlining
common
among
clusters.
Moreover,
further
data
higher
risk
ALS
professional
athletes
and,
particular,
soccer
football
players.
Despite
this
increased
highlighted
by
evidence
aforementioned
sports,
remain
unclear.
At
last,
use
raw
water
has
been
associated
risk.
aim
present
review
is
characterize
possible
relationship
between
clusters,
be
explored
context
interaction
genetic
Molecular Neurodegeneration,
Год журнала:
2023,
Номер
18(1)
Опубликована: Май 4, 2023
Amyotrophic
lateral
sclerosis
is
a
complex
disorder
most
of
which
'sporadic'
unknown
origin
but
approximately
10%
familial,
arising
from
single
mutations
in
any
more
than
30
genes.
Thus,
there
are
familial
ALS
subtypes,
with
different,
often
unknown,
molecular
pathologies
leading
to
constellation
clinical
phenotypes.
We
have
mouse
models
for
many
genetic
forms
the
disorder,
these
do
not,
on
their
own,
necessarily
show
us
key
pathological
pathways
at
work
human
patients.
To
date,
we
no
90%
that
'sporadic'.
Potential
therapies
been
developed
mainly
using
limited
set
models,
and
through
lack
alternatives,
past
tested
patients
regardless
aetiology.
Cancer
researchers
undertaken
therapy
development
similar
challenges;
they
responded
by
producing
transformed
understanding
processes,
implemented
patient
stratification
multi-centre
trials,
effective
translation
basic
research
findings
clinic.
successfully
adopted
this
combined
approach,
now
increase
our
disease
pathologies,
rate
progress
moving
mechanism
need
more,
innovative,
address
specific
questions.
Current Opinion in Neurology,
Год журнала:
2024,
Номер
37(5), С. 560 - 569
Опубликована: Июль 5, 2024
Purpose
of
review
Amyotrophic
lateral
sclerosis
(ALS)
has
a
strong
genetic
basis,
but
the
landscape
ALS
appears
to
be
complex.
The
purpose
this
article
is
recent
developments
in
genetics
ALS.
Recent
findings
Large-scale
studies
have
uncovered
more
than
40
genes
contributing
susceptibility.
Both
rare
variants
with
variable
effect
size
and
common
small
been
identified.
most
are
C9orf72
,
SOD1
TARDBP
FUS
.
Some
causative
shared
frontotemporal
dementia,
confirming
molecular
link
between
both
diseases.
Access
diagnostic
gene
testing
for
improve,
as
effective
silencing
therapies
some
subtypes
emerging,
there
no
consensus
about
which
test
for.
Summary
Our
knowledge
basis
improved
first
specific
underway.
These
therapeutic
advances
underline
need
better
access
people
Further
research
needed
further
map
heterogeneity
establish
best
strategy
clinical
setting.
Neurotherapeutics,
Год журнала:
2022,
Номер
19(4), С. 1133 - 1144
Опубликована: Июль 1, 2022
This
review
addresses
the
longstanding
debate
over
whether
amyotrophic
lateral
sclerosis
(ALS)
is
a
'dying
back'
or
forward'
disorder
in
light
of
new
gene
identifications
and
increased
understanding
mechanisms
action
for
previously
identified
ALS
genes.
While
topological
pattern
pathology
animal
models,
more
anecdotally
patients
indeed
back',
this
discusses
how
fits
with
fact
that
many
major
initiating
events
are
thought
to
occur
within
soma.
It
also
widely
varying
risk
factors,
including
some
impacting
axons
directly,
may
combine
drive
common
pathway
involving
TAR
DNA
binding
protein
43
(TDP-43)
neuromuscular
junction
(NMJ)
denervation.
The
emerging
association
between
sterile
alpha
TIR
motif-containing
1
(SARM1),
so
far
mostly
associated
axon
degeneration,
sporadic
another
theme.
strengths
limitations
current
evidence
supporting
an
considered,
along
ways
which
SARM1
could
become
activated
ALS.
final
section
SARM1-based
therapies
prospects
targeting
other
axonal
steps
pathogenesis.
