Frontiers in Aging Neuroscience,
Год журнала:
2019,
Номер
11
Опубликована: Март 19, 2019
Astrocytes,
one
of
the
largest
glial
cell
population
in
Central
Nervous
System,
play
key
function
several
events
brain
development
and
function,
such
as
synapse
formation
control
neurotransmitters
release
uptake,
production
trophic
factors
neuronal
survival.
Initially
described
a
homogenous
population,
evidences
have
pointed
that
astrocytes
are
highly
heterogeneous,
both
morphologically
functionally,
within
same
region,
across
different
regions.
Recent
findings
suggest
heterogeneity
expression
profile
proteins
involved
astrocyte
may
predict
selective
vulnerability
regions
to
specific
diseases,
well
age-related
cognitive
decline.
However,
molecular
mechanisms
underlying
these
changes,
either
aging
disease
scarce.
Neuroinflammation,
hallmark
neurodegenerative
diseases
aging,
is
reported
dubious
impact
on
activation,
cells
pro-
anti-inflammatory
cytokines
chemokines,
anti-oxidants,
free
radicals,
neurotrophic
factors.
Despite
emerging
evidence
supporting
reactive
duality
their
phenotype,
neurotoxic
or
neuroprotective
properties,
depending
age
stimuli,
cellular
interplays
regional
still
matter
discussion.
In
this
review,
we
will
summarize
recent
phenotypes,
likely
for
during
neural
diseases.
We
focus
molecules
triggered
by
Finally,
discuss
new
how
modulation
phenotype
could
synaptic
deficits
dysfunction
present
pathological
states.
Physiological Reviews,
Год журнала:
2018,
Номер
99(1), С. 21 - 78
Опубликована: Окт. 3, 2018
The
blood-brain
barrier
(BBB)
prevents
neurotoxic
plasma
components,
blood
cells,
and
pathogens
from
entering
the
brain.
At
same
time,
BBB
regulates
transport
of
molecules
into
out
central
nervous
system
(CNS),
which
maintains
tightly
controlled
chemical
composition
neuronal
milieu
that
is
required
for
proper
functioning.
In
this
review,
we
first
examine
molecular
cellular
mechanisms
underlying
establishment
BBB.
Then,
focus
on
physiology,
endothelial
pericyte
transporters,
perivascular
paravascular
transport.
Next,
discuss
rare
human
monogenic
neurological
disorders
with
primary
genetic
defect
in
BBB-associated
cells
demonstrating
link
between
breakdown
neurodegeneration.
review
effects
genes
inheritance
and/or
increased
susceptibility
Alzheimer's
disease
(AD),
Parkinson's
(PD),
Huntington's
disease,
amyotrophic
lateral
sclerosis
(ALS)
relation
to
other
pathologies
deficits.
We
next
how
dysfunction
relates
deficits
majority
sporadic
AD,
PD,
ALS
cases,
multiple
sclerosis,
neurodegenerative
disorders,
acute
CNS
such
as
stroke,
traumatic
brain
injury,
spinal
cord
epilepsy.
Lastly,
BBB-based
therapeutic
opportunities.
conclude
lessons
learned
future
directions,
emphasis
technological
advances
investigate
functions
living
brain,
at
level,
address
key
unanswered
questions.
Journal of Alzheimer s Disease,
Год журнала:
2018,
Номер
64(s1), С. S567 - S610
Опубликована: Июнь 12, 2018
The
amyloid-
oligomer
(AO)
hypothesis
was
introduced
in
1998.It
proposed
that
the
brain
damage
leading
to
Alzheimer's
disease
(AD)
instigated
by
soluble,
ligand-like
AOs.This
based
on
discovery
fibril-free
synthetic
preparations
of
AOs
were
potent
CNS
neurotoxins
rapidly
inhibited
long-term
potentiation
and,
with
time,
caused
selective
nerve
cell
death
(Lambert
et
al.,
1998).The
mechanism
attributed
disrupted
signaling
involving
tyrosine-protein
kinase
Fyn,
mediated
an
unknown
toxin
receptor.Over
4,000
articles
concerning
have
been
published
since
then,
including
more
than
400
reviews.AOs
shown
accumulate
AD-dependent
manner
human
and
animal
model
tissue
experimentally,
impair
learning
memory
instigate
major
facets
AD
neuropathology,
tau
pathology,
synapse
deterioration
loss,
inflammation,
oxidative
damage.As
reviewed
Hayden
Teplow
2013,
AO
"has
all
but
supplanted
amyloid
cascade."Despite
emerging
understanding
role
played
pathogenesis,
not
yet
received
clinical
attention
given
plaques,
which
at
core
attempts
therapeutics
diagnostics
are
no
longer
regarded
as
most
pathogenic
form
A.However,
if
momentum
research
continues,
particularly
efforts
elucidate
key
aspects
structure,
a
clear
path
successful
modifying
therapy
can
be
envisioned.Ensuring
lessons
learned
from
recent,
late-stage
failures
applied
appropriately
throughout
therapeutic
development
will
further
enable
likelihood
near-term.
British Journal of Pharmacology,
Год журнала:
2018,
Номер
175(16), С. 3190 - 3199
Опубликована: Янв. 10, 2018
In
mammals,
a
central
circadian
clock,
located
in
the
suprachiasmatic
nuclei
(SCN)
of
hypothalamus,
tunes
innate
physiological
rhythms
to
ambient
24
h
light-dark
cycle
invigorate
and
optimize
internal
temporal
order.
The
SCN-activated,
light-inhibited
production
melatonin
conveys
message
darkness
clock
induces
night-state
functions,
for
example,
sleep/wake
blood
pressure
metabolism.
Clinically
meaningful
effects
treatment
have
been
demonstrated
placebo-controlled
trials
humans,
particularly
disorders
associated
with
diminished
or
misaligned
rhythms,
rhythm-related
sleep
disorders,
jet
lag
shift
work,
insomnia
children
neurodevelopmental
poor
(non-restorative)
quality,
non-dipping
nocturnal
(nocturnal
hypertension)
Alzheimer's
disease
(AD).
at
very
early
stages
AD,
role
restorative
value
(perceived
quality)
its
sleep-anticipating
resulting
attenuated
activation
certain
brain
networks
are
gaining
new
perspective
as
quality
build-up
β
amyloid,
precuneus,
is
unravelled.
As
result
recently
discovered
relationship
between
neurodegeneration,
prospects
using
intervention,
promote
healthy
physical
mental
ageing,
prime
interest
view
emerging
link
aetiology
disease.
LINKED
ARTICLES:
This
article
part
themed
section
on
Recent
Developments
Research
Melatonin
Potential
Therapeutic
Applications.
To
other
articles
this
visit
http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.16/issuetoc.
Annual Review of Pathology Mechanisms of Disease,
Год журнала:
2017,
Номер
13(1), С. 379 - 394
Опубликована: Дек. 1, 2017
The
central
nervous
system
(CNS)
is
unique
in
being
the
only
organ
lacking
lymphatic
vessels
to
assist
removal
of
interstitial
metabolic
waste
products.
Recent
work
has
led
discovery
glymphatic
system,
a
glial-dependent
perivascular
network
that
subserves
pseudolymphatic
function
brain.
Within
pathway,
cerebrospinal
fluid
(CSF)
enters
brain
via
periarterial
spaces,
passes
into
interstitium
astrocytic
aquaporin-4,
and
then
drives
perivenous
drainage
(ISF)
its
solute.
Here,
we
review
role
pathway
CNS
physiology,
factors
known
regulate
flow,
pathologic
processes
which
breakdown
CSF-ISF
exchange
been
implicated
disease
initiation
progression.
Important
areas
future
research,
including
manipulation
activity
aiming
improve
clearance
therapeutic
agent
delivery,
are
also
discussed.
