Brain,
Год журнала:
2017,
Номер
140(12), С. 3252 - 3268
Опубликована: Окт. 5, 2017
The
Dlg4
gene
encodes
for
post-synaptic
density
protein
95
(PSD95),
a
major
synaptic
that
clusters
glutamate
receptors
and
is
critical
plasticity.
PSD95
levels
are
diminished
in
ageing
neurodegenerative
disorders,
including
Alzheimer's
disease
Huntington's
disease.
epigenetic
mechanisms
(dys)regulate
transcription
of
Dlg4/PSD95,
or
other
plasticity
genes,
largely
unknown,
limiting
the
development
targeted
epigenome
therapy.
We
analysed
Dlg4/PSD95
landscape
hippocampal
tissue
designed
gene-targeting
strategy:
zinc
finger
DNA-binding
domain
was
engineered
fused
to
effector
domains
either
repress
(G9a,
Suvdel76,
SKD)
activate
(VP64)
transcription,
generating
artificial
factors
editors
(methylating
H3K9).
These
epi-editors
altered
histone
marks
subsequently
expression,
which,
importantly,
impacted
several
neuron
processes.
Intriguingly,
transduction
factor
PSD95-VP64
rescued
memory
deficits
aged
mice.
Conclusively,
this
work
validates
as
key
player
establishes
editing
potential
therapy
treat
human
neurological
disorders.
International Journal of Nanomedicine,
Год журнала:
2019,
Номер
Volume 14, С. 5541 - 5554
Опубликована: Июль 1, 2019
Abstract:
Currently,
47
million
people
live
with
dementia
globally,
and
it
is
estimated
to
increase
more
than
threefold
(∼131
million)
by
2050.
Alzheimer's
disease
(AD)
one
of
the
major
causative
factors
induce
progressive
dementia.
AD
a
neurodegenerative
disease,
its
pathogenesis
has
been
attributed
extracellular
aggregates
amyloid
β
(Aβ)
plaques
intracellular
neurofibrillary
tangles
made
hyperphosphorylated
τ-protein
in
cortical
limbic
areas
human
brain.
It
characterized
memory
loss
neurocognitive
dysfunction.
The
anomalous
processing
APP
β-secretases
γ-secretases
leads
production
Aβ
40
42
monomers,
which
further
oligomerize
aggregate
into
senile
plaques.
also
intensifies
through
infectious
agents
like
HIV.
Additionally,
during
pathogenesis,
presence
high
concentrations
peptides
central
nervous
system
initiates
microglial
infiltration.
Upon
coming
vicinity
Aβ,
microglia
get
activated,
endocytose
contribute
toward
their
clearance
via
TREM2
surface
receptors,
simultaneously
triggering
innate
immunoresponse
against
aggregation.
In
addition
detailed
report
on
leading
AD,
present
review
discusses
current
state
art
therapeutics
diagnostics,
including
labeling
imaging
techniques
employed
as
contrast
for
better
visualization
sensing
points
an
urgent
need
nanotechnology
efficient
therapeutic
strategy
bioavailability
drugs
system.
Keywords:
beta,
amyloidogenesis,
precursor
proteins,
β-secretases,
γ-secretases,
tau
phosphorylation
Genes Brain & Behavior,
Год журнала:
2013,
Номер
13(1), С. 69 - 86
Опубликована: Ноя. 28, 2013
To
date,
there
is
rapidly
increasing
evidence
for
host-microbe
interaction
at
virtually
all
levels
of
complexity,
ranging
from
direct
cell-to-cell
communication
to
extensive
systemic
signalling,
and
involving
various
organs
organ
systems,
including
the
central
nervous
system.
As
such,
discovery
that
differential
microbial
composition
associated
with
alterations
in
behaviour
cognition
has
significantly
contributed
establishing
microbiota-gut-brain
axis
as
an
extension
well-accepted
gut-brain
concept.
Many
efforts
have
been
focused
on
delineating
a
role
this
health
disease,
stress-related
disorders
such
depression,
anxiety
irritable
bowel
syndrome
neurodevelopmental
autism.
There
also
growing
appreciation
epigenetic
mechanisms
shaping
brain
behaviour.
However,
epigenetics
informing
interactions
received
little
attention
date.
This
despite
fact
are
many
plausible
routes
between
host-microbiota
dialogue.
From
new
perspective
we
put
forward
novel,
yet
testable,
hypotheses.
Firstly,
suggest
gut-microbial
products
can
affect
chromatin
plasticity
within
their
host's
turn
leads
changes
neuronal
transcription
eventually
alters
host
Secondly,
argue
microbiota
important
mediator
gene-environment
interactions.
Finally,
reason
itself
may
be
viewed
entity.
In
conclusion,
fields
(neuro)epigenetics
microbiology
converging
more
interdisciplinary
studies
necessary
unravel
full
range
interaction.
Science,
Год журнала:
2014,
Номер
346(6209), С. 572 - 578
Опубликована: Окт. 30, 2014
Human
cognitive
aging
differs
between
and
is
malleable
within
individuals.
In
the
absence
of
a
strong
genetic
program,
it
open
to
host
hazards,
such
as
vascular
conditions,
metabolic
syndrome,
chronic
stress,
but
also
protective
enhancing
factors,
experience-dependent
plasticity.
Longitudinal
studies
suggest
that
leading
an
intellectually
challenging,
physically
active,
socially
engaged
life
may
mitigate
losses
consolidate
gains.
Interventions
help
identify
contexts
mechanisms
successful
give
science
society
hint
about
what
would
be
possible
if
conditions
were
different.
