Journal of Translational Medicine,
Год журнала:
2023,
Номер
21(1)
Опубликована: Фев. 9, 2023
Recent
numerous
epidemiology
and
clinical
association
studies
reported
that
ApoE
polymorphism
might
be
associated
with
the
risk
severity
of
coronavirus
disease
2019
(COVID-19),
yielded
inconsistent
results.
Severe
acute
respiratory
syndrome
2
(SARS-CoV-2)
infection
relies
on
its
spike
protein
binding
to
angiotensin-converting
enzyme
(ACE2)
receptor
expressed
host
cell
membranes.A
meta-analysis
was
conducted
clarify
between
COVID-19.
Multiple
interaction
assays
were
utilized
investigate
potential
molecular
link
SARS-CoV-2
primary
ACE2,
protein.
Immunoblotting
immunofluorescence
staining
methods
used
access
regulatory
effect
different
isoform
ACE2
expression.ApoE
gene
(ε4
carrier
genotypes
VS
non-ε4
genotypes)
is
increased
(P
=
0.0003,
OR
1.44,
95%
CI
1.18-1.76)
progression
<
0.00001,
1.85,
1.50-2.28)
interacts
both
but
did
not
show
isoform-dependent
effects.
ApoE4
significantly
downregulates
expression
in
vitro
vivo
subsequently
decreases
conversion
Ang
II
1-7.ApoE4
increases
infectivity
a
manner
may
depend
differential
interactions
or
ACE2.
Instead,
dysregulation
renin-angiotensin
system
(RAS)
provide
explanation
by
which
exacerbates
COVID-19
disease.
Alzheimer s Research & Therapy,
Год журнала:
2020,
Номер
12(1)
Опубликована: Дек. 1, 2020
COVID-19
is
primarily
a
respiratory
disease
but
up
to
two
thirds
of
hospitalised
patients
show
evidence
central
nervous
system
(CNS)
damage,
predominantly
ischaemic,
in
some
cases
haemorrhagic
and
occasionally
encephalitic.
It
unclear
how
much
the
ischaemic
damage
mediated
by
direct
or
inflammatory
effects
virus
on
CNS
vasculature
secondary
extracranial
cardiorespiratory
disease.
Limited
data
suggest
that
causative
SARS-CoV-2
may
enter
via
nasal
mucosa
olfactory
fibres,
haematogenous
spread,
capable
infecting
endothelial
cells,
pericytes
probably
neurons.
Extracranially,
targets
cells
pericytes,
causing
cell
dysfunction,
vascular
leakage
immune
activation,
sometimes
leading
disseminated
intravascular
coagulation.
remains
be
confirmed
whether
cerebral
are
similarly
targeted.
Several
aspects
likely
impact
cognition.
Cerebral
white
matter
particularly
vulnerable
also
critically
important
for
cognitive
function.
There
accumulating
hypoperfusion
accelerates
amyloid-β
(Aβ)
accumulation
linked
tau
TDP-43
pathology,
inducing
phosphorylation
α-synuclein
at
serine-129,
ischaemia
increase
risk
development
Lewy
body
Current
therapies
understandably
focused
supporting
function,
preventing
thrombosis
reducing
activation.
Since
angiotensin-converting
enzyme
(ACE)-2
receptor
SARS-CoV-2,
ACE
inhibitors
angiotensin
blockers
predicted
ACE-2
expression,
it
was
initially
feared
their
use
might
exacerbate
COVID-19.
Recent
meta-analyses
have
instead
suggested
these
medications
protective.
This
perhaps
because
entry
deplete
ACE-2,
tipping
balance
towards
II-ACE-1-mediated
classical
RAS
activation:
exacerbating
promoting
inflammation.
relevant
APOE
ε4
individuals,
who
seem
increased
COVID-19,
lowest
activity.
leave
an
unexpected
legacy
long-term
neurological
complications
significant
number
survivors.
Cognitive
follow-up
will
important,
especially
develop
cerebrovascular
during
acute
illness.
Cellular and Molecular Neurobiology,
Год журнала:
2020,
Номер
42(1), С. 217 - 224
Опубликована: Авг. 25, 2020
The
gateway
for
invasion
by
the
novel
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2)
into
human
host
cells
is
via
angiotensin-converting
enzyme
(ACE2)
transmembrane
receptor
expressed
in
multiple
immune
and
nonimmune
cell
types.
SARS-CoV-2,
that
causes
disease
2019
(COVID-19;
CoV-19)
has
unusual
capacity
to
attack
many
different
types
of
simultaneously
clathrin-
caveolae-independent
endocytic
pathways,
becoming
injurious
diverse
cells,
tissues
organ
systems
exploiting
any
weakness
host.
elicitation
this
multipronged
explains
part
severity
extensive
variety
signs
symptoms
observed
CoV-19
patients.
To
further
our
understanding
mechanism
pathways
SARS-CoV-2
infection
susceptibility
specific
cell-
tissue-types
communication
we
analyzed
ACE2
expression
85
including
21
brain
regions,
7
fetal
8
controls.
Besides
strong
respiratory,
digestive,
renal-excretory
reproductive
high
was
also
found
amygdala,
cerebral
cortex
brainstem.
highest
level
pons
medulla
oblongata
brainstem,
containing
medullary
centers
brain,
may
explain
patients
distress.
International Journal of Molecular Sciences,
Год журнала:
2020,
Номер
21(12), С. 4471 - 4471
Опубликована: Июнь 23, 2020
The
signaling
pathway
of
the
microtubule-associated
protein
kinase
or
extracellular
regulated
(MAPK/ERK)
is
a
common
mechanism
information
transduction
from
stimuli
to
intracellular
space.
leads
changes
in
ongoing
metabolic
pathways
and
modification
gene
expression
patterns.
In
central
nervous
system,
ERK
expressed
ubiquitously,
both
temporally
spatially.
As
for
temporal
ubiquity,
this
system
participates
three
key
moments:
(i)
Embryonic
development;
(ii)
early
postnatal
period;
iii)
adulthood.
During
embryonic
development,
partly
responsible
patterning
segmentation
encephalic
vesicle
through
FGF8-ERK
pathway.
addition,
during
period,
directs
neurogenesis
migration
final
fate
neural
progenitors.
maturation
process
dendritic
trees
synaptogenesis.
adulthood,
social
emotional
behavior
memory
processes,
including
long-term
potentiation.
Alterations
mechanisms
related
are
associated
with
different
pathological
outcomes.
Genetic
alterations
any
component
result
pathologies
crest
derivatives
mental
dysfunctions
autism
spectrum
disorders.
MAP-ERK
element
neuroinflammatory
triggered
by
glial
cells
development
neurodegenerative
diseases,
such
as
Parkinson's
Alzheimer's
disease,
Huntington's
amyotrophic
lateral
sclerosis,
well
prionic
diseases.
MAPK/ERK
activation
depends
on
stage
(mature
senescence),
type
cellular
which
activated,
anatomic
structure.
However,
extensive
gaps
exist
regards
targets
phosphorylated
many
these
processes.
Cell,
Год журнала:
2023,
Номер
186(5), С. 906 - 922
Опубликована: Фев. 2, 2023
ACE2
is
the
indispensable
entry
receptor
for
SARS-CoV
and
SARS-CoV-2.
Because
of
COVID-19
pandemic,
it
has
become
one
most
therapeutically
targeted
human
molecules
in
biomedicine.
serves
two
fundamental
physiological
roles:
as
an
enzyme,
alters
peptide
cascade
balance;
a
chaperone,
controls
intestinal
amino
acid
uptake.
ACE2's
tissue
distribution,
affected
by
co-morbidities
sex,
explains
broad
tropism
coronaviruses
clinical
manifestations
SARS
COVID-19.
ACE2-based
therapeutics
provide
universal
strategy
to
prevent
treat
SARS-CoV-2
infections,
applicable
all
variants
other
emerging
zoonotic
exploiting
their
cellular
receptor.
Fluids and Barriers of the CNS,
Год журнала:
2021,
Номер
18(1)
Опубликована: Июль 14, 2021
Abstract
Background
SARS-CoV-2,
a
coronavirus
(CoV),
is
known
to
cause
acute
respiratory
distress
syndrome,
and
number
of
non-respiratory
complications,
particularly
in
older
male
patients
with
prior
health
conditions,
such
as
obesity,
diabetes
hypertension.
These
conditions
are
associated
vascular
dysfunction,
the
CoV
disease
2019
(COVID-19)
complications
include
multiorgan
failure
neurological
problems.
While
main
route
entry
into
body
inhalation,
this
virus
has
been
found
many
tissues,
including
choroid
plexus
meningeal
vessels,
neurons
CSF.
Main
We
reviewed
SARS-CoV-2/COVID-19,
ACE2
distribution
beneficial
effects,
CNS
barriers,
possible
mechanisms
by
which
enters
brain,
outlined
(obesity,
hypertension
diabetes),
COVID-19
manifestation
aging
cerebrovascualture.
The
overall
aim
provide
general
reader
breadth
information
on
type
wide
its
receptor
so
better
understand
significance
uniqueness
pre-existing
medical
that
affect
brain.
issue
there
no
sound
evidence
for
large
flux
SARS-CoV-2
at
present,
compared
invasion
inhalation
pathways.
Conclusions
detected
brains
from
severely
infected
patients,
it
unclear
how
gets
there.
There
brain
significantly
contribute
outcomes
once
system
invaded
virus.
consensus,
based
normal
infection
presence
olfactory
mucosa
Studies
needed
demonstrate
replication
parenchyma
neuroinvasion.
It
manifestations
consequence
mainly
cardio-respiratory
failure.
Understanding
potential
neuroinvasion
pathways
could
help
define
COVID-19.
Hypertension,
Год журнала:
2021,
Номер
78(3), С. 629 - 643
Опубликована: Июнь 21, 2021
Hypertension
is
an
established
risk
factor
for
cognitive
decline
and
dementia
in
older
adults,
highlighting
the
potential
importance
of
antihypertensive
treatments
prevention
efforts.
Work
surrounding
has
suggested
possible
salutary
effects
on
cognition
neuropathology.
Several
studies
have
specifically
highlighted
renin-angiotensin
system
drugs,
including
AT1-receptor
blockers
angiotensin-converting-enzyme
inhibitors,
as
potentially
benefiting
later
life.
A
small
number
further
drugs
that
cross
blood-brain
barrier
may
be
linked
to
lower
compared
their
nonpenetrant
counterparts.
The
present
meta-analysis
sought
evaluate
benefits
crossing
relative
We
harmonized
longitudinal
participant
data
from
14
cohorts
6
countries
(Australia,
Canada,
Germany,
Ireland,
Japan,
United
States),
a
total
12
849
individuals
at
baseline,
assessed
within
medications
used
by
cognitively
normal
participants.
analyzed
7
domains
(attention,
executive
function,
language,
verbal
memory
learning,
recall,
mental
status,
processing
speed)
using
ANCOVA
(adjusted
age,
sex,
education)
meta-analyses.
Older
adults
taking
barrier-crossing
exhibited
better
recall
over
up
3
years
follow-up,
those
medications,
despite
relatively
higher
vascular
burden.
Conversely,
nonblood-brain
barrier-penetrant
showed
attention
same
follow-up
period,
although
burden
partially
explain
this
result.
Findings
suggest
links
between
less
decline.
Ageing Research Reviews,
Год журнала:
2022,
Номер
77, С. 101612 - 101612
Опубликована: Март 26, 2022
Alzheimer's
disease
(AD)
is
a
well-known
neurodegenerative
characterized
by
the
presence
of
two
main
hallmarks
–
Tau
hyperphosphorylation
and
Aβ
deposits.
Notwithstanding,
in
last
few
years
scientific
evidence
about
drivers
AD
have
been
changing
nowadays
age-related
vascular
alterations
several
cardiovascular
risk
factors
shown
to
trigger
development
AD.
In
this
context,
drugs
targeting
Renin
Angiotensin
System
(RAS),
commonly
used
for
treatment
hypertension,
are
evidencing
high
potential
delay
due
their
action
on
brain
RAS.
Indeed,
ACE
1/Ang
II/AT1R
axis
believed
be
upregulated
responsible
deleterious
effects
such
as
increased
oxidative
stress,
neuroinflammation,
blood-brain
barrier
(BBB)
hyperpermeability,
astrocytes
dysfunction
decrease
cerebral
blood
flow.
contrast,
alternative
II/AT2R;
2/Ang
(1−7)/MasR;
Ang
IV/
AT4R(IRAP)
seems
counterbalance
principal
exert
beneficial
memory
cognition.
Accordingly,
retrospective
studies
demonstrate
reduced
developing
among
people
taking
RAS
medication
well
vitro
vivo
pre-clinical
it
herein
critically
reviewed.
review,
we
first
revise,
at
glance,
pathophysiology
focused
its
classic
hallmarks.
Secondly,
an
overview
impact
also
provided,
four
essential
axes
II/AT1R.
Finally,
therapeutic
available
AD,
namely
angiotensin
II
receptor
blockers
(ARBs)
converting
enzyme
inhibitors
(ACEIs),
highlighted
data
supporting
hope
will
presented,
from
clinical
studies.
Translational Neurodegeneration,
Год журнала:
2022,
Номер
11(1)
Опубликована: Сен. 11, 2022
Coronavirus
disease
2019
(COVID-19),
which
is
caused
by
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2),
a
life-threatening
disease,
especially
in
elderly
individuals
and
those
with
comorbidities.
The
predominant
clinical
manifestation
of
COVID-19
dysfunction,
while
neurological
presentations
are
increasingly
being
recognized.
SARS-CoV-2
invades
host
cells
primarily
via
attachment
the
spike
protein
to
angiotensin-converting
enzyme
(ACE2)
receptor
expressed
on
cell
membranes.
Patients
Alzheimer's
(AD)
more
susceptible
infection
prone
outcomes.
Recent
studies
have
revealed
some
common
risk
factors
for
AD
COVID-19.
An
understanding
association
between
potential
related
mechanisms
may
lead
development
novel
approaches
treating
both
diseases.
In
present
review,
we
first
summarize
central
nervous
system
(CNS)
then
discuss
associations
shared
key
AD,
focus
ACE2
receptor,
apolipoprotein
E
(APOE)
genotype,
age,
neuroinflammation.
International Journal of Environmental Research and Public Health,
Год журнала:
2023,
Номер
20(3), С. 2146 - 2146
Опубликована: Янв. 25, 2023
Alzheimer’s
disease
(AD)
is
a
life-changing
condition
whose
etiology
explained
by
several
hypotheses.
Recently,
new
virus
contributed
to
the
evidence
of
viral
involvement
in
AD:
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2),
which
causes
COVID-19
disease.
AD
was
found
be
one
most
common
comorbidities,
and
it
increase
mortality
from
this
as
well.
Moreover,
patients
were
observed
present
with
distinct
clinical
features
COVID-19,
delirium
being
prevalent
group.
The
SARS-CoV-2
enters
host
cells
through
angiotensin-converting
enzyme
(ACE2)
receptor.
ACE2
overexpressed
brains
AD,
thus
increases
invasion.
Furthermore,
inhibition
receptor
may
also
decrease
brain-derived
neurotrophic
factor
(BDNF),
contributing
neurodegeneration.
ApoE
ε4
allele,
risk
facilitate
entry
into
cells.
neuroinflammation
oxidative
stress
existing
enhance
inflammatory
response
associated
COVID-19.
pandemic
social
distancing
measures
negatively
affected
mental
health,
cognitive
function,
neuro-psychiatric
symptoms
patients.
This
review
comprehensively
covers
links
between
disease,
including
presentation,
molecular
mechanisms,
effects
distancing.