Frontal Cortex Lipid Alterations During the Onset of Alzheimer’s Disease
Journal of Alzheimer s Disease,
Год журнала:
2024,
Номер
98(4), С. 1515 - 1532
Опубликована: Апрель 2, 2024
Background:
Although
sporadic
Alzheimer’s
disease
(AD)
is
a
neurodegenerative
disorder
of
unknown
etiology,
familial
AD
associated
with
specific
gene
mutations.
A
commonality
between
these
forms
that
both
display
multiple
pathogenic
events
including
cholinergic
and
lipid
dysregulation.
Objective:
We
aimed
to
identify
the
relevant
lipids
activity
their
related
receptors
in
frontal
cortex
correlating
them
cognition
during
progression
AD.
Methods:
MALDI-mass
spectrometry
imaging
(MSI)
functional
autoradiography
was
used
evaluate
distribution
phospholipids/sphingolipids
cannabinoid
1
(CB1),
sphingosine
1-phosphate
(S1P1),
muscarinic
M2/M4
(FC)
people
come
autopsy
premortem
clinical
diagnosis
AD,
mild
cognitive
impairment
(MCI),
no
(NCI).
Results:
MALDI-MSI
revealed
an
increase
myelin-related
lipids,
such
as
diacylglycerol
(DG)
36:1,
DG
38:5,
phosphatidic
acid
(PA)
40:6
white
matter
(WM)
MCI
compared
NCI,
downregulation
WM
phosphatidylinositol
(PI)
38:4
PI
38:5
levels
NCI.
Elevated
phosphatidylcholine
(PC)
32:1,
PC
34:0,
sphingomyelin
38:1
were
observed
discrete
accumulations
FC
supragranular
layers
progression.
Muscarinic
receptor
activation
V-VI
decreased
MCI.
CB1
upregulated
V-VI,
while
S1P1
downregulated
within
relative
Conclusions:
lipidomic
alterations
are
myelin
dyshomeostasis
prodromal
suggesting
maintenance
potential
therapeutic
target
for
dementia.
Язык: Английский
Neurolipid systems: A new target for the treatment of dementia
Basic & Clinical Pharmacology & Toxicology,
Год журнала:
2024,
Номер
135(3), С. 225 - 236
Опубликована: Июль 22, 2024
Abstract
Neurolipids
comprise
a
diverse
class
of
bioactive
lipids
that
include
molecules
capable
activating
G
protein‐coupled
receptors,
thereby
inducing
systemic
effects
contribute
to
the
maintenance
homeostasis.
Dementia,
non‐specific
brain
disorder
characterized
by
common
set
signs
and
symptoms,
usually
arises
subsequent
injuries
or
diseases
is
often
associated
with
aging
process.
Individuals
affected
dementia
suffer
from
disruption
several
neurotransmitter
neuromodulatory
systems,
among
which
neurolipids
play
an
important
role,
including
endocannabinoid,
lysophosphatidic
acid
sphingosine
1‐phosphate
systems.
In
this
review,
we
present
overview
most
recent
pertinent
findings
regarding
involvement
these
neurolipidic
systems
in
dementia,
data
wide
range
both
vitro
vivo
experiments
as
well
clinical
trials.
Язык: Английский
Cognitive improvement via cortical cannabinoid receptors and choline‐containing lipids
British Journal of Pharmacology,
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 3, 2024
Background
and
Purpose
Recent
research
linking
choline‐containing
lipids
to
degeneration
of
basal
forebrain
cholinergic
neurons
in
neuropathological
states
illustrates
the
challenge
balancing
lipid
integrity
with
optimal
acetylcholine
levels,
essential
for
memory
preservation.
The
endocannabinoid
system
influences
learning
processes
regulated
by
neurotransmission.
Therefore,
we
hypothesised
that
activation
may
confer
neuroprotection
against
degeneration.
Experimental
Approach
We
examined
neuroprotective
potential
sub‐chronic
treatments
cannabinoid
agonist
WIN55,212‐2,
using
ex
vivo
organotypic
tissue
cultures
including
nucleus
basalis
magnocellularis
cortex
rat
models
specific
damage
induced
192IgG‐saporin.
Levels
lipids,
choline
were
measured
histochemical
immunofluorescence
assays,
along
[
35
S]GTPγS
autoradiography
muscarinic
GPCRs
MALDI‐mass
spectrometry
imaging
analysis.
Learning
assessed
Barnes
maze
novel
object
recognition
test
rats
3xTg‐AD
mouse
model.
Key
Results
Degeneration,
192IgG‐saporin,
baso‐cortical
pathways
resulted
deficits
decreased
cortical
levels
lysophosphatidylcholines
(LPC).
WIN55,212‐2
restored
transmission
LPC
via
receptors.
This
altered
homeostasis
mainly
reducing
sphingomyelins
lesioned
animals.
These
modifications
crucial
recovery.
Conclusion
Implications
hypothesise
facilitates
an
alternative
source
breaking
down
sphingomyelins,
leading
elevated
LPCs.
results
imply
altering
receptors
presents
a
promising
therapeutic
approach
dementia
linked
dysfunction.
Язык: Английский
Alterations in protein quality control resulting in neurodegeneration and disease
Elsevier eBooks,
Год журнала:
2025,
Номер
unknown, С. 123 - 175
Опубликована: Янв. 1, 2025
Язык: Английский
The emerging role of endocannabinoid system modulation in human fibroblast-like synoviocytes: Exploring new biomarkers and potential therapeutic targets
Biomedicine & Pharmacotherapy,
Год журнала:
2025,
Номер
186, С. 118040 - 118040
Опубликована: Апрель 10, 2025
Язык: Английский
Exploring Membrane Cholesterol Binding to the CB1 Receptor: A Computational Perspective
The Journal of Physical Chemistry B,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 23, 2025
Cholesterol
(CHOL)
is
a
potential
allosteric
modulator
of
the
CB1
receptor.
In
this
work,
we
use
atomistic
molecular
dynamics
simulations
to
study
how
CHOL
interacts
with
and
identify
its
binding
sites
(BS)
residence
times
on
specific
receptor
zones.
Our
results
evince
minimal
changes
in
conformational
secondary
structure
due
CHOL.
We
report
five
BSs,
three
which
coincide
previously
described
interaction
regions
(BS1,
BS2,
BS3),
while
BS4
BS5
are
proposed
as
new
BSs.
Quantum
descriptors
bonding
such
Natural
Bond
Orbitals
(NBO),
Theory
Atoms
Molecules
(QTAIM),
Noncovalent
Interactions
(NCI)
analyses
employed
characterize
CHOL-BS
interactions.
The
show
an
exponential
correlation
between
strength
interactions
(mainly
hydrogen
bonds
hydrophobic
contacts)
time
at
Although
other
approaches
exist
high-affinity
protein
sites,
our
methodology
integrates
classical
quantum
descriptions
better
BSs
predict
ligand
CB1,
distinguishing
persistent
from
transitory
contacts.
Since
has
been
suggested
endogenous
ligand,
flexible
strategy
allows
studying
that
stabilize
could
be
extended
cannabinoid
binding,
contribute
designing
improved
ligands.
Язык: Английский
Dysregulated Neurotransmitters and CB1 Receptor Dysfunction and Their Roles in Agitation Associated with Alzheimer’s Disease
Journal of dementia and Alzheimer's disease,
Год журнала:
2025,
Номер
2(2), С. 15 - 15
Опубликована: Июнь 1, 2025
Alzheimer’s
disease
(AD)
is
characterized
by
the
progressive
loss
of
cognitive
function
and
frequently
accompanied
neuropsychiatric
symptoms
(NPS).
Pathologically,
AD
defined
two
hallmark
features:
extracellular
accumulation
β-amyloid
intracellular
hyperphosphorylation
tau
protein.
In
addition
to
these
primary
changes,
several
other
abnormalities
are
associated
with
disease,
including
neuroinflammation,
synaptic
loss,
oxidative
stress,
neurotransmitter
imbalance,
genetic
epigenetic
alterations.
NPS
in
encompass
a
range
symptoms,
such
as
anxiety,
apathy,
agitation,
depression,
psychosis.
These
thought
arise
partly
from
damage
caused
pathological
hallmarks
AD,
which
impair
various
systems.
Altered
levels
neurotransmitters,
gamma-aminobutyric
acid
(GABA),
serotonin
(5-HT),
dopamine
(DA),
cholinergic
noradrenergic
systems,
have
been
implicated
development
agitation.
Additionally,
reduced
endocannabinoid
system
(ECS)
functionality,
particularly
cannabinoid
receptor
1
(CB1R),
has
linked
neurobehavioral
Preclinical
studies
suggest
that
decrease
CB1R
aggressive
behavior,
agonists
demonstrated
beneficial
effects
alleviating
agitation
related
symptoms.
Given
findings,
current
review
focuses
on
therapeutic
potential
targeting
systems
dysfunction
manage
AD.
Язык: Английский
Exploring the therapeutic potential of natural compounds modulating the endocannabinoid system in various diseases and disorders: review
Pharmacological Reports,
Год журнала:
2023,
Номер
75(6), С. 1410 - 1444
Опубликована: Окт. 31, 2023
Язык: Английский
Exploratory survey study on adjunctive use of medical cannabis for Gaucher disease
Rare Disease and Orphan Drugs Journal,
Год журнала:
2024,
Номер
3(3)
Опубликована: Авг. 23, 2024
Aims
:
Using
an
investigator-designed
survey
tool
to
confirm
that
adult
patients
with
type
1
Gaucher
disease
(GD1)
often
self-prescribe
cannabis
products
try
alleviate
symptoms
such
as
lingering
fatigue,
chronic
bone
and
joint
pain,
loss
of
energy,
anxiety,
depression
persist
despite
enzyme
replacement
therapy
(ERT)
or
substrate
restriction
(SRT).
Additionally,
explore
whether
patient
reports
symptom
relief
adverse
side
effects
relate
frequency
duration
use.
Methods
We
conducted
anonymous,
cross-sectional
questionnaire
study
elicit
GD1
patient-reported
experiences
used
they
attributed
their
underlying
disease.
Eligible
participants
included
individuals
aged
≥
18
years,
regardless
sex,
gender,
country
residence,
ethnicity,
state
health
treatment
status.
The
questions
basic
socio-demography
(n
=
9),
GD
diagnosis
pre-treatment
signs
16),
information
current
12),
concurrent
manifestations
Parkinson’s
6),
details
use
24),
perceived
effect
on
13),
interest
in
participating
future
studies
2).
Results:
159
adults
(81.5%
US)
responded
advertisements
online
sites
informational
posts
advocacy
group
newsletters.
most
frequent
were
fatigue
(83.8%),
pain
(79.7%),
bleeding
problems
(73.0%).
Hemostasis
substantially
improved,
but
achiness,
anxiety
persisted.
Sixty-two
respondents
(39%)
reported
very
heterogeneous
There
was
a
positive
association
between
the
severity
persistent
likelihood
Cannabis
users
improvements
muscle
(84.3%),
(82.4%),
(70.6%),
general
achiness
(66.7%).
However,
moderate
extreme
manifestations,
breathing
problems,
memory
loss,
episodic
dyscoordination
more
prevalent
among
inhaled
than
non-users.
Conclusion:
Our
results
justify
further
investigations
determine
efficacy
safety
specifically
for
patients.
Although
randomized
controlled
trials
would
be
optimal,
well-designed
observational
registry
may
practical
approach.
some
reluctant
talk
openly
doctors
about
cannabis,
should
routinely
queried
by
primary
care
physicians
specialists
who,
turn,
must
able
provide
informed
guidance
safety,
dosage,
potential
interactions
other
medications
is
using.
Язык: Английский
Investigation in the cannabigerol derivative VCE-003.2 as a disease-modifying agent in a mouse model of experimental synucleinopathy
Behavioral and Brain Functions,
Год журнала:
2024,
Номер
20(1)
Опубликована: Ноя. 1, 2024
The
cannabigerol
derivative
VCE-003.2,
which
has
activity
at
the
peroxisome
proliferator-activated
receptor-γ
afforded
neuroprotection
in
experimental
models
of
Parkinson's
disease
(PD)
based
on
mitochondrial
dysfunction
(6-hydroxydopamine-lesioned
mice)
and
neuroinflammation
(LPS-lesioned
mice).
Now,
we
aim
to
explore
VCE-003.2
neuroprotective
properties
a
PD
model
that
also
involves
protein
dysregulation,
other
key
event
pathogenesis.
Язык: Английский