Homocysteine Metabolites, Endothelial Dysfunction, and Cardiovascular Disease
International Journal of Molecular Sciences,
Journal Year:
2025,
Volume and Issue:
26(2), P. 746 - 746
Published: Jan. 16, 2025
Atherosclerosis
is
accompanied
by
inflammation
that
underlies
cardiovascular
disease
(CVD)
and
its
vascular
manifestations,
including
acute
stroke,
myocardial
infarction,
peripheral
artery
disease,
the
leading
causes
of
morbidity/mortality
worldwide.
The
monolayer
endothelial
cells
formed
on
luminal
surface
arteries
veins
regulates
tone
permeability,
which
supports
homeostasis.
Endothelial
dysfunction,
first
step
in
development
atherosclerosis,
caused
mechanical
biochemical
factors
disrupt
homeostasis
induce
inflammation.
Together
with
increased
plasma
levels
low-density
lipoprotein
(LDL),
diabetes,
hypertension,
cigarette
smoking,
infectious
microorganisms,
genetic
factors,
epidemiological
studies
established
dysregulated
metabolism
homocysteine
(Hcy)
causing
hyperhomocysteinemia
(HHcy)
associated
CVD.
Patients
severe
HHcy
exhibit
CVD
die
prematurely
due
to
complications.
Biochemically,
characterized
elevated
Hcy
related
metabolites
such
as
Hcy-thiolactone
N-Hcy-protein,
seen
nutritional
deficiencies
humans
animals.
only
known
source
methionine
released
gut
from
dietary
protein.
generated
S-adenosylhomocysteine
(AdoHcy)
metabolized
cystathionine
β-synthase
(CBS)
methionyl-tRNA
synthetase.
Hcy-thiolactone,
a
chemically
reactive
thioester,
modifies
protein
lysine
residues,
generating
N-homocysteinylated
(N-Hcy)-protein.
N-Hcy-proteins
lose
their
normal
native
function
become
cytotoxic,
autoimmunogenic,
proinflammatory,
prothrombotic,
proatherogenic.
Accumulating
evidence,
discussed
this
review,
shows
these
can
promote
CVD,
stroke
inducing
pro-atherogenic
changes
gene
expression,
upregulating
mTOR
signaling,
inhibiting
autophagy
through
epigenetic
mechanisms
involving
specific
microRNAs,
histone
demethylase
PHF8,
methylated
H4K20me1.
Clinical
studies,
also
show
are
infarction
ischemic
influencing
blood
clotting.
These
findings
contribute
our
understanding
complex
underlying
identify
potential
targets
for
therapeutic
intervention.
Language: Английский
The Neonatal Microbiome: Implications for Amyotrophic Lateral Sclerosis and Other Neurodegenerations
Brain Sciences,
Journal Year:
2025,
Volume and Issue:
15(2), P. 195 - 195
Published: Feb. 14, 2025
Most
brain
development
occurs
in
the
"first
1000
days",
a
critical
period
from
conception
to
child's
second
birthday.
Critical
processes
that
occur
during
this
time
include
synaptogenesis,
myelination,
neural
pruning,
and
formation
of
functioning
neuronal
circuits.
Perturbations
first
days
likely
contribute
later-life
neurodegenerative
disease,
including
sporadic
amyotrophic
lateral
sclerosis
(ALS).
Neurodevelopment
is
determined
by
many
events,
maturation
colonization
infant
microbiome
its
metabolites,
specifically
neurotransmitters,
immune
modulators,
vitamins,
short-chain
fatty
acids.
Successful
gut-brain
axis
function
depend
on
maternal
factors
(stress
exposure
toxins
pregnancy),
mode
delivery,
quality
postnatal
environment,
diet
after
weaning
breast
milk,
nutritional
deficiencies.
While
neonatal
highly
plastic,
it
remains
prone
dysbiosis
which,
once
established,
may
persist
into
adulthood,
thereby
inducing
chronic
inflammation
abnormal
excitatory/inhibitory
balance,
resulting
excitation.
Both
are
recognized
as
key
pathophysiological
ALS.
Language: Английский
Research Progress on Glial Cells in Neurodegenerative Diseases
Journal of Contemporary Medical Practice,
Journal Year:
2025,
Volume and Issue:
7(2), P. 18 - 23
Published: Feb. 28, 2025
This
review
discusses
glial
cells
in
neurodegenerative
diseases
as
represents
their
role
and
scientific
advances.
Glial
specifically
offer
support
to
neurons
all
fields
of
normal
functioning
while
also
participating
processes
such
damage
repair
under
pathological
minutiae.
The
article
the
above
with
respect
Alzheimer’s,
Parkinson’s,
multiple
sclerosis,
other
ailments
by
combining
latest
research
findings
discuss
potential
therapeutic
targets
intervention
avenues.
It
emphasizes
that
understanding
cell
functions
engages
can
be
critical
they
develop
novel
treatment
approaches
for
debilitating
conditions.
Language: Английский