Current Medicinal Chemistry,
Journal Year:
2021,
Volume and Issue:
29(24), P. 4138 - 4151
Published: Nov. 30, 2021
Alzheimer's
disease
(AD)
is
the
most
common
form
of
dementia
worldwide,
with
approximately
6
million
cases
reported
in
America
2020.
The
clinical
signs
AD
include
cognitive
dysfunction,
apathy,
anxiety
and
neuropsychiatric
signs,
pathogenetic
mechanisms
that
involve
amyloid
peptide-β
extracellular
accumulation
tau
hyperphosphorylation.
Unfortunately,
current
drugs
to
treat
can
provide
only
symptomatic
relief
but
are
not
disease-modifying
molecules
able
revert
progression.
endogenous
modulator
adenosine,
through
A2A
receptor
activation,
plays
a
role
synaptic
loss
neuroinflammation,
which
crucial
for
impairment
memory
damage.In
this
review,
recent
advances
covering
adenosine
antagonists
will
be
extensively
reviewed,
providing
basis
rational
design
future
inhibitors.Herein,
literature
on
receptors
their
plasticity
as
well
effects
antagonism
animal
models
humans,
reviewed.
Furthermore,
chemical
structure-based
strategies
presented.Caffeine,
widely
consumed
natural
product
stimulant
an
antagonist,
improves
human
memory.
Similarly,
synthetic
antagonists,
described
may
means
fight
AD.This
review
highlights
potential
novel
approach
patients
AD.
Cells,
Journal Year:
2023,
Volume and Issue:
12(3), P. 454 - 454
Published: Jan. 31, 2023
Aducanumab,
co-developed
by
Eisai
(Japan)
and
Biogen
(U.S.),
has
received
Food
Drug
Administration
approval
for
treating
Alzheimer’s
disease
(AD).
In
addition,
its
successor
antibody,
lecanemab,
been
approved.
These
antibodies
target
the
aggregated
form
of
small
peptide,
amyloid-β
(Aβ),
which
accumulates
in
patient
brain.
The
“amyloid
hypothesis”
based
therapy
that
places
aggregation
toxicity
Aβ
at
center
etiology
is
about
to
be
realized.
However,
effects
immunotherapy
are
still
limited,
suggesting
need
reconsider
this
hypothesis.
produced
from
a
type-I
transmembrane
protein,
precursor
protein
(APP).
One
APP
metabolites,
99-amino
acids
C-terminal
fragment
(C99,
also
called
βCTF),
direct
AD
patient’s
brain
demonstrate
independent
Aβ.
Conventional
drug
discovery
strategies
have
focused
on
“outside”
neuron,
but
C99
accumulation
might
explain
“inside”
was
overlooked
Furthermore,
common
region
promising
multifunctional
drugs.
This
review
aimed
outline
nature,
metabolism,
impact
pathogenesis
discuss
whether
it
could
therapeutic
complementing
amyloid
Current Medicinal Chemistry,
Journal Year:
2021,
Volume and Issue:
29(24), P. 4138 - 4151
Published: Nov. 30, 2021
Alzheimer's
disease
(AD)
is
the
most
common
form
of
dementia
worldwide,
with
approximately
6
million
cases
reported
in
America
2020.
The
clinical
signs
AD
include
cognitive
dysfunction,
apathy,
anxiety
and
neuropsychiatric
signs,
pathogenetic
mechanisms
that
involve
amyloid
peptide-β
extracellular
accumulation
tau
hyperphosphorylation.
Unfortunately,
current
drugs
to
treat
can
provide
only
symptomatic
relief
but
are
not
disease-modifying
molecules
able
revert
progression.
endogenous
modulator
adenosine,
through
A2A
receptor
activation,
plays
a
role
synaptic
loss
neuroinflammation,
which
crucial
for
impairment
memory
damage.In
this
review,
recent
advances
covering
adenosine
antagonists
will
be
extensively
reviewed,
providing
basis
rational
design
future
inhibitors.Herein,
literature
on
receptors
their
plasticity
as
well
effects
antagonism
animal
models
humans,
reviewed.
Furthermore,
chemical
structure-based
strategies
presented.Caffeine,
widely
consumed
natural
product
stimulant
an
antagonist,
improves
human
memory.
Similarly,
synthetic
antagonists,
described
may
means
fight
AD.This
review
highlights
potential
novel
approach
patients
AD.
