GeroScience,
Journal Year:
2020,
Volume and Issue:
43(3), P. 1135 - 1158
Published: Oct. 10, 2020
Abstract
In
2009,
rapamycin
was
reported
to
increase
the
lifespan
of
mice
when
implemented
later
in
life.
This
observation
resulted
a
sea-change
how
researchers
viewed
aging.
first
evidence
that
pharmacological
agent
could
have
an
impact
on
aging
administered
life,
i.e.,
intervention
did
not
be
early
life
before
negative
Over
past
decade,
there
has
been
explosion
number
reports
studying
effect
various
diseases,
physiological
functions,
and
biochemical
processes
mice.
this
review,
we
focus
those
areas
which
is
strong
for
rapamycin’s
age-related
diseases
mice,
e.g.,
lifespan,
cardiac
disease/function,
central
nervous
system,
immune
cell
senescence.
We
conclude
it
time
pre-clinical
studies
focused
taking
clinic,
as
potential
treatment
Alzheimer’s
disease.
Journal of Biological Chemistry,
Journal Year:
2010,
Volume and Issue:
285(17), P. 13107 - 13120
Published: Feb. 24, 2010
Accumulation
of
amyloid-β
(Aβ)
and
Tau
is
an
invariant
feature
Alzheimer
disease
(AD).
The
upstream
role
Aβ
accumulation
in
the
pathogenesis
widely
accepted,
there
strong
evidence
showing
that
causes
cognitive
impairments.
However,
molecular
mechanisms
linking
to
decline
remain
be
elucidated.
Here
we
show
buildup
increases
mammalian
target
rapamycin
(mTOR)
signaling,
whereas
decreasing
mTOR
signaling
reduces
levels,
thereby
highlighting
interrelation
between
Aβ.
pathway
plays
a
central
controlling
protein
homeostasis
hence,
neuronal
functions;
indeed
regulates
different
forms
learning
memory.
Using
animal
model
AD,
pharmacologically
restoring
with
rescues
deficits
ameliorates
pathology
by
increasing
autophagy.
Indeed,
further
autophagy
induction
necessary
for
rapamycin-mediated
reduction
levels.
results
presented
here
provide
basis
Aβ-induced
and,
moreover,
rapamycin,
FDA
approved
drug,
improves
memory
pathology.
Annual Review of Neuroscience,
Journal Year:
2012,
Volume and Issue:
35(1), P. 529 - 558
Published: May 20, 2012
Despite
being
regarded
as
a
hippie
science
for
decades,
cannabinoid
research
has
finally
found
its
well-deserved
position
in
mainstream
neuroscience.
A
series
of
groundbreaking
discoveries
revealed
that
endocannabinoid
molecules
are
widespread
and
important
conventional
neurotransmitters
such
glutamate
or
GABA,
yet
they
act
profoundly
unconventional
ways.
We
aim
to
illustrate
how
uncovering
the
molecular,
anatomical,
physiological
characteristics
signaling
new
mechanistic
insights
into
several
fundamental
phenomena
synaptic
physiology.
First,
we
summarize
unexpected
advances
molecular
complexity
biogenesis
inactivation
two
endocannabinoids,
anandamide
2-arachidonoylglycerol.
Then,
show
these
metabolic
routes
integrated
well-known
intracellular
pathways.
These
endocannabinoid-producing
signalosomes
operate
phasic
tonic
modes,
thereby
differentially
governing
homeostatic,
short-term,
long-term
plasticity
throughout
brain.
Finally,
discuss
cell
type-
synapse-specific
refinement
may
explain
characteristic
behavioral
effects
cannabinoids.
Glia,
Journal Year:
2010,
Volume and Issue:
58(9), P. 1017 - 1030
Published: March 29, 2010
CB1
and
CB2
receptors
are
activated
by
a
plethora
of
cannabinoid
compounds,
be
they
endogenously-produced,
plant-derived
or
synthetic.
These
expressed
microglia,
astrocytes
astrocytomas,
their
activation
regulates
these
cells'
differentiation,
functions
viability.
Recent
studies
show
that
glial
cells
also
express
cannabinoid-like
receptors,
different
cell
functions,
but
control
This
review
summarizes
this
evidence,
discusses
how
selective
compounds
targeting
constitute
promising
therapeutics
to
manage
neuroinflammation
eradicate
malignant
astrocytomas.
Importantly,
the
should
provide
therapeutic
relieve
without
inducing
typical
psychotropic
effects
possible
addictive
properties
associated
with
use
Delta9-tetrahydrocannabinol,
main
ingredient
produced
plant
Cannabis
sativa.
Brain,
Journal Year:
2014,
Volume and Issue:
138(1), P. 94 - 109
Published: Nov. 11, 2014
Anti-N-methyl
D-aspartate
receptor
(NMDAR)
encephalitis
is
a
severe
neuropsychiatric
disorder
that
associates
with
prominent
memory
and
behavioural
deficits.
Patients'
antibodies
react
the
N-terminal
domain
of
GluN1
(previously
known
as
NR1)
subunit
NMDAR
causing
in
cultured
neurons
selective
reversible
internalization
cell-surface
receptors.
These
effects
frequent
response
to
immunotherapy
have
suggested
an
antibody-mediated
pathogenesis,
but
date
there
no
animal
model
showing
patients'
cause
To
develop
such
model,
C57BL6/J
mice
underwent
placement
ventricular
catheters
connected
osmotic
pumps
delivered
continuous
infusion
or
control
cerebrospinal
fluid
(flow
rate
0.25
µl/h,
14
days).
During
after
period
standardized
tests
were
applied,
including
tasks
assess
(novel
object
recognition
open
field
V-maze
paradigms),
anhedonic
behaviours
(sucrose
preference
test),
depressive-like
(tail
suspension,
forced
swimming
tests),
anxiety
(black
white,
elevated
plus
maze
aggressiveness
(resident-intruder
locomotor
activity
(horizontal
vertical).
Animals
sacrificed
at
Days
5,
13,
18,
26
46
examined
for
brain-bound
antibody
on
total
synaptic
clusters
protein
concentration
using
confocal
microscopy
immunoblot
analysis.
experiments
showed
animals
infused
fluid,
not
developed
progressive
deficits,
behaviours,
without
affecting
other
tasks.
Memory
deficits
gradually
worsened
until
Day
18
(4
days
stopped)
all
symptoms
resolved
over
next
week.
Accompanying
brain
tissue
studies
increase
human
antibodies,
predominantly
hippocampus
(maximal
13–18),
acid
extraction
characterization
GluN1-expressing
embryonic
kidney
cells
confirmed
be
against
NMDAR.
Confocal
analysis
decrease
density
18),
post-synaptic
95
(PSD95)
α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic
(AMPA)
occurred
parallel
improved
reversibility
accompanied
by
restoration
levels.
Overall,
these
findings
establish
link
between
reduction
NMDAR,
provide
biological
basis
which
removal
antibody-producing
improve
neurological
function,
offer
testing
experimental
therapies
this
similar
disorders.
