Frontiers in Neuroscience,
Год журнала:
2019,
Номер
13
Опубликована: Июнь 21, 2019
Alzheimer
disease
(AD)
represents
an
oncoming
epidemic
that
without
effective
treatment
promises
to
exact
extraordinary
human
and
financial
burdens.
Studies
of
pathogenesis
are
essential
for
defining
targets
discovering
disease-modifying
treatments.
Past
studies
AD
neuropathology
provided
valuable,
albeit
limited,
insights.
Nevertheless,
building
on
these
findings,
recent
have
increasingly
rich
harvest
genetic,
molecular
cellular
data
creating
unprecedented
opportunities
both
understand
treat
AD.
Among
the
most
significant
those
documenting
presence
within
brain
toxic
oligomeric
species
Aβ
tau.
Existing
support
view
such
can
propagate
spread
neural
circuits.
To
place
findings
in
context
we
first
review
genetics
AD,
including
Down
syndrome.
We
detail
existence
while
noting
unanswered
questions
concerning
their
precise
structures,
means
by
which
they
undergo
amplification
how
induce
neuronal
dysfunction
degeneration.
conclude
offering
a
speculative
synthesis
oligomers
tau
initiate
drive
pathogenesis.
While
100
years
after
Alzheimer's
report
there
is
much
still
learn
about
discovery
treatments,
application
new
concepts
sophisticated
tools
poised
deliver
important
advances
combatting
Neural Plasticity,
Год журнала:
2016,
Номер
2016, С. 1 - 15
Опубликована: Янв. 1, 2016
Alzheimer’s
disease
(AD)
currently
presents
one
of
the
biggest
healthcare
issues
in
developed
countries.
There
is
no
effective
treatment
capable
slowing
down
progression.
In
recent
years
main
focus
research
on
novel
pharmacotherapies
was
based
amyloidogenic
hypothesis
AD,
which
posits
that
beta
amyloid
(A
β
)
peptide
chiefly
responsible
for
cognitive
impairment
and
neuronal
death.
The
goal
such
treatments
(a)
to
reduce
A
production
through
inhibition
γ
secretase
enzymes
(b)
promote
dissolution
existing
cerebral
plaques.
However,
this
approach
has
proven
be
only
modestly
effective.
Recent
studies
suggest
an
alternative
strategy
centred
downstream
signalling,
particularly
at
synapse.
oligomers
may
cause
aberrant
N-methyl-D-aspartate
receptor
(NMDAR)
activation
postsynaptically
by
forming
complexes
with
cell-surface
prion
protein
(PrPC).
PrPC
enriched
postsynaptic
density,
where
it
interacts
Fyn
tyrosine
kinase.
occurs
when
bound
PrPC-Fyn
complex.
causes
phosphorylation
NR2B
subunit
metabotropic
glutamate
5
(mGluR5).
kinase
blockers
masitinib
saracatinib
have
efficacious
treating
AD
symptoms
experimental
mouse
models
disease.
Frontiers in Neuroscience,
Год журнала:
2019,
Номер
13
Опубликована: Июнь 21, 2019
Alzheimer
disease
(AD)
represents
an
oncoming
epidemic
that
without
effective
treatment
promises
to
exact
extraordinary
human
and
financial
burdens.
Studies
of
pathogenesis
are
essential
for
defining
targets
discovering
disease-modifying
treatments.
Past
studies
AD
neuropathology
provided
valuable,
albeit
limited,
insights.
Nevertheless,
building
on
these
findings,
recent
have
increasingly
rich
harvest
genetic,
molecular
cellular
data
creating
unprecedented
opportunities
both
understand
treat
AD.
Among
the
most
significant
those
documenting
presence
within
brain
toxic
oligomeric
species
Aβ
tau.
Existing
support
view
such
can
propagate
spread
neural
circuits.
To
place
findings
in
context
we
first
review
genetics
AD,
including
Down
syndrome.
We
detail
existence
while
noting
unanswered
questions
concerning
their
precise
structures,
means
by
which
they
undergo
amplification
how
induce
neuronal
dysfunction
degeneration.
conclude
offering
a
speculative
synthesis
oligomers
tau
initiate
drive
pathogenesis.
While
100
years
after
Alzheimer's
report
there
is
much
still
learn
about
discovery
treatments,
application
new
concepts
sophisticated
tools
poised
deliver
important
advances
combatting
