ACS Pharmacology & Translational Science,
Journal Year:
2024,
Volume and Issue:
8(1), P. 47 - 65
Published: Dec. 30, 2024
Sigma
1
receptor
(S1R)
is
a
multifunctional,
ligand-activated
protein
located
in
the
membranes
of
endoplasmic
reticulum
(ER).
It
mediates
variety
neurological
disorders,
including
epilepsy,
amyotrophic
lateral
sclerosis,
Alzheimer's
disease,
Huntington's
disease.
The
wide
neuroprotective
effects
S1R
agonists
are
achieved
by
pro-survival
and
antiapoptotic
S1R-mediated
signaling
functions.
Nonetheless,
relatively
little
known
about
specific
molecular
mechanisms
underlying
activity.
Many
studies
on
have
highlighted
importance
maintaining
normal
cellular
homeostasis
through
its
control
calcium
lipid
exchange
between
ER
mitochondria,
ER-stress
response,
many
other
mechanisms.
In
this
review,
we
will
discuss
different
localization
explain
S1R-associated
biological
activity,
such
as
ER-plasma
membrane
Mitochondrion-Associated
Membrane
interfaces.
While
outlining
important
binding
partners
involved
these
processes,
also
explained
how
dysregulation
pathways
contributes
to
neurodegenerative
disorders.
Livers,
Journal Year:
2024,
Volume and Issue:
4(4), P. 615 - 637
Published: Nov. 28, 2024
Long
regarded
as
illicit
substances
with
no
clinical
value,
N-dimethylated
tryptamines—such
N,N-dimethyltryptamine,
5-methoxy-N,N-dimethyltryptamine,
and
bufotenine—have
been
found
to
produce
naturally
in
a
wide
variety
of
species,
including
humans.
Known
for
their
psychoactive
effects
through
serotonin
receptors
(5-HTRs),
tryptamines
are
currently
being
reinvestigated
clinically
long-term
benefits
mental
disorders.
Endogenous
tryptamine
is
methylated
by
indolethylamine-N-methyltransferase
(INMT),
which
can
then
serve
an
agonist
pro-survival
pathways,
such
sigma
non-opioid
intracellular
receptor
1
(SIGMAR1)
signaling.
Fibrogenic
diseases,
like
metabolic-associated
fatty
liver
disease
(MAFLD),
steatohepatitis
(MASH),
chronic
kidney
(CKD)
have
shown
changes
INMT
SIGMAR1
activity
the
progression
pathogenesis.
At
cellular
level,
endothelial
cells
fibroblasts
express
various
tissues;
however,
little
known
about
injury
fibrosis.
In
this
review,
I
will
give
overview
biochemistry,
molecular
biology,
current
evidence
INMT’s
role
hepatic
fibrogenesis.
also
discuss
pre-clinical
findings
N-methylated
highlight
new
upcoming
therapeutic
strategies
that
may
be
adapted
mitigating
fibrogenic
diseases.
Finally,
mention
recent
mutualistic
gut
bacteria
influencing
endogenous
signaling
metabolism.
ACS Pharmacology & Translational Science,
Journal Year:
2024,
Volume and Issue:
8(1), P. 47 - 65
Published: Dec. 30, 2024
Sigma
1
receptor
(S1R)
is
a
multifunctional,
ligand-activated
protein
located
in
the
membranes
of
endoplasmic
reticulum
(ER).
It
mediates
variety
neurological
disorders,
including
epilepsy,
amyotrophic
lateral
sclerosis,
Alzheimer's
disease,
Huntington's
disease.
The
wide
neuroprotective
effects
S1R
agonists
are
achieved
by
pro-survival
and
antiapoptotic
S1R-mediated
signaling
functions.
Nonetheless,
relatively
little
known
about
specific
molecular
mechanisms
underlying
activity.
Many
studies
on
have
highlighted
importance
maintaining
normal
cellular
homeostasis
through
its
control
calcium
lipid
exchange
between
ER
mitochondria,
ER-stress
response,
many
other
mechanisms.
In
this
review,
we
will
discuss
different
localization
explain
S1R-associated
biological
activity,
such
as
ER-plasma
membrane
Mitochondrion-Associated
Membrane
interfaces.
While
outlining
important
binding
partners
involved
these
processes,
also
explained
how
dysregulation
pathways
contributes
to
neurodegenerative
disorders.
