Biochemical Pharmacology,
Journal Year:
2023,
Volume and Issue:
211, P. 115522 - 115522
Published: March 28, 2023
Alzheimer's
disease
(AD)
is
one
of
the
most
prevalent
neurodegenerative
diseases
that
affect
millions
people
worldwide,
with
both
prevalence
and
incidence
increasing
age.
It
characterized
by
cognitive
decline
associated,
specifically,
degeneration
cholinergic
neurons.
The
problem
this
even
more
fundamental
as
available
therapies
remain
fairly
limited
mainly
focused
on
symptoms'
relief.
Although
aetiology
remains
elusive,
two
main
pathological
hallmarks
are
described:
i)
presence
neurofibrillary
tangles
formed
unfolded
protein
aggregates
(hyperphosphorylated
Tau
protein)
ii)
extracellular
amyloid-beta
peptide.
Given
complexity
surrounding
pathogenesis
disease,
several
potential
targets
have
been
highlighted
interrelated
upon
its
progression,
such
oxidative
stress
accumulation
metal
ions.
Thus,
advances
made
development
innovative
multitarget
therapeutical
compounds
to
delay
progression
restore
cell
function.
This
review
focuses
ongoing
research
new
insights
emerging
disease-modifying
drugs
for
AD
treatment.
Furthermore,
classical
novel
biomarkers
early
diagnosis
their
role
in
assisting
improvement
targeted
will
also
be
approached.
Signal Transduction and Targeted Therapy,
Journal Year:
2021,
Volume and Issue:
6(1)
Published: Nov. 8, 2021
Abstract
In
recent
years,
accumulating
evidence
has
elucidated
the
role
of
lysosomes
in
dynamically
regulating
cellular
and
organismal
homeostasis.
Lysosomal
changes
dysfunction
have
been
correlated
with
development
numerous
diseases.
this
review,
we
interpreted
key
biological
functions
four
areas:
metabolism,
cell
proliferation
differentiation,
immunity,
death.
More
importantly,
actively
sought
to
determine
characteristic
cells
affected
by
these
diseases,
causes
dysfunction,
their
significance
treatment
human
disease.
Furthermore,
outlined
currently
available
targeting
strategies:
(1)
lysosomal
acidification;
(2)
cathepsins;
(3)
membrane
permeability
integrity;
(4)
calcium
signaling;
(5)
mTOR
(6)
emerging
potential
strategies.
Moreover,
systematically
summarized
corresponding
drugs
application
clinical
trials.
By
integrating
basic
research
findings,
discussed
current
opportunities
challenges
Alzheimer s & Dementia,
Journal Year:
2022,
Volume and Issue:
19(4), P. 1403 - 1414
Published: Sept. 24, 2022
Abstract
Introduction
Plasma
biomarkers
will
likely
revolutionize
the
diagnostic
work‐up
of
Alzheimer's
disease
(AD)
globally.
Before
widespread
use,
we
need
to
determine
if
confounding
factors
affect
levels
these
biomarkers,
and
their
clinical
utility.
Methods
Participants
with
plasma
CSF
creatinine,
body
mass
index
(BMI),
medical
history
data
were
included
(BioFINDER‐1:
n
=
748,
BioFINDER‐2:
421).
We
measured
beta‐amyloid
(Aβ42,
Aβ40),
phosphorylated
tau
(p‐tau217,
p‐tau181),
neurofilament
light
(NfL),
glial
fibrillary
acidic
protein
(GFAP).
Results
In
both
cohorts,
creatinine
BMI
main
associated
NfL,
GFAP,
a
lesser
extent
p‐tau.
However,
adjustment
for
had
only
minor
effects
in
models
predicting
either
corresponding
or
subsequent
development
dementia.
Discussion
Creatinine
are
related
certain
levels,
but
they
do
not
have
clinically
relevant
vast
majority
individuals.
Highlights
(BMI)
biomarker
levels.
Adjusting
has
influence
on
plasma‐cerebrospinal
fluid
(CSF)
associations.
prediction
dementia
using
biomarkers.
Frontiers in Immunology,
Journal Year:
2021,
Volume and Issue:
12
Published: Sept. 16, 2021
Neuroinflammation
play
an
important
role
in
Alzheimer’s
disease
pathogenesis.
Advances
molecular
imaging
using
positron
emission
tomography
have
provided
insights
into
the
time
course
of
neuroinflammation
and
its
relation
with
central
pathologies
patients
animal
models.
Recent
single-cell
sequencing
transcriptomics
indicate
dynamic
disease-associated
microglia
astrocyte
profiles
disease.
Mitochondrial
18-kDa
translocator
protein
is
most
widely
investigated
target
for
imaging.
New
generation
tracers
improved
performance
been
developed
evaluated
along
tau
amyloid
assessing
progression
continuum.
Given
that
not
exclusively
expressed
glia,
alternative
targets
are
under
rapid
development,
such
as
monoamine
oxidase
B,
matrix
metalloproteinases,
colony-stimulating
factor
1
receptor,
imidazoline-2
binding
sites,
cyclooxygenase,
cannabinoid-2
purinergic
P2X7
P2Y12
fractalkine
triggering
receptor
on
myeloid
cells
2,
advanced
glycation
end
products.
Promising
should
demonstrate
a
higher
specificity
cellular
locations
exclusive
expression
or
activation
status
(pro-
anti-inflammatory)
highly
specific
ligand
to
enable
vivo
brain
In
this
review,
we
summarised
recent
advances
development
outlook
promising
future.
Biochemical Pharmacology,
Journal Year:
2023,
Volume and Issue:
211, P. 115522 - 115522
Published: March 28, 2023
Alzheimer's
disease
(AD)
is
one
of
the
most
prevalent
neurodegenerative
diseases
that
affect
millions
people
worldwide,
with
both
prevalence
and
incidence
increasing
age.
It
characterized
by
cognitive
decline
associated,
specifically,
degeneration
cholinergic
neurons.
The
problem
this
even
more
fundamental
as
available
therapies
remain
fairly
limited
mainly
focused
on
symptoms'
relief.
Although
aetiology
remains
elusive,
two
main
pathological
hallmarks
are
described:
i)
presence
neurofibrillary
tangles
formed
unfolded
protein
aggregates
(hyperphosphorylated
Tau
protein)
ii)
extracellular
amyloid-beta
peptide.
Given
complexity
surrounding
pathogenesis
disease,
several
potential
targets
have
been
highlighted
interrelated
upon
its
progression,
such
oxidative
stress
accumulation
metal
ions.
Thus,
advances
made
development
innovative
multitarget
therapeutical
compounds
to
delay
progression
restore
cell
function.
This
review
focuses
ongoing
research
new
insights
emerging
disease-modifying
drugs
for
AD
treatment.
Furthermore,
classical
novel
biomarkers
early
diagnosis
their
role
in
assisting
improvement
targeted
will
also
be
approached.
