Unveiling the Therapeutic Potential of Folate-Dependent One-Carbon Metabolism in Cancer and Neurodegeneration
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(17), С. 9339 - 9339
Опубликована: Авг. 28, 2024
Cellular
metabolism
is
crucial
for
various
physiological
processes,
with
folate-dependent
one-carbon
(1C)
playing
a
pivotal
role.
Folate,
B
vitamin,
key
cofactor
in
this
pathway,
supporting
DNA
synthesis,
methylation
and
antioxidant
defenses.
In
dividing
cells,
folate
facilitates
nucleotide
biosynthesis,
ensuring
genomic
stability
preventing
carcinogenesis.
Additionally,
neurodevelopment,
essential
neural
tube
closure
central
nervous
system
formation.
Thus,
dysregulation
of
can
contribute
to
pathologies
such
as
cancer,
severe
birth
defects,
neurodegenerative
diseases.
Epidemiological
evidence
highlights
folate's
impact
on
disease
risk
its
potential
therapeutic
target.
antifolate
drugs
that
inhibit
enzymes
1C
strategies
targeting
receptors
are
current
options.
However,
cancer
complex,
varying
among
types
dietary
contexts.
conditions,
including
Alzheimer's
Parkinson's
diseases,
deficiency
exacerbates
cognitive
decline
through
elevated
homocysteine
levels,
contributing
neuronal
damage.
Clinical
trials
folic
acid
supplementation
show
mixed
outcomes,
underscoring
the
complexities
neuroprotective
effects.
This
review
integrates
knowledge
neurodegeneration,
exploring
molecular
mechanisms,
clinical
implications,
strategies,
which
provide
information
advancing
treatments.
Язык: Английский
Association of Methyl Donor Nutrients’ Dietary Intake and Cognitive Impairment in the Elderly Based on the Intestinal Microbiome
Nutrients,
Год журнала:
2024,
Номер
16(13), С. 2061 - 2061
Опубликована: Июнь 28, 2024
Globally,
cognitive
impairment
(CI)
is
the
leading
cause
of
disability
and
dependency
among
elderly,
presenting
a
significant
public
health
concern.
However,
there
currently
deficiency
in
pharmacological
interventions
that
can
effectively
cure
or
significantly
reverse
progression
impairment.
Methyl
donor
nutrients
(MDNs),
including
folic
acid,
choline,
vitamin
B12,
have
been
identified
as
potential
enhancers
function.
Nevertheless,
remains
dearth
comprehensive
research
investigating
connection
between
dietary
intake
MDNs
CI.
In
our
study,
we
comprehensively
assessed
relationship
MDNs’
CI
older
adults,
utilizing
16S
rRNA
gene
sequencing
to
investigate
underlying
mechanisms.
The
results
showed
an
obvious
difference
methyl-donor
nutritional
quality
index
(MNQI)
dementia
(D)
group
dementia-free
(DF)
group.
Specifically,
was
lower
MNQI
D
than
DF
For
gut
microbiome,
beta
diversity
flora
exhibited
higher
levels
high
(HQ)
opposed
low
(LQ)
group,
comparison
Subsequently,
performed
correlation
analysis
examine
relative
abundance
microbiota,
MDNs,
Montreal
Cognitive
Assessment
(MoCA)
scores,
ultimately
identifying
ten
genera
with
regulatory
functions.
Additionally,
KEGG
pathway
analyses
suggested
one-carbon
metabolism,
chronic
inflammation,
DNA
synthesis
potentially
serve
pathways
through
which
may
be
promising
for
influencing
These
implied
might
enhance
function
regulation
microbiota
homeostasis.
This
study
offers
recommendations
prevention
management
elderly.
Язык: Английский
The epigenetic approach of varicocele: a focus on sperm DNA and m6A-RNA methylation
Human Reproduction Update,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 13, 2024
Abstract
BACKGROUND
Varicocele
is
an
abnormal
dilation
and
torsion
of
the
pampiniform
venous
plexus
in
scrotum
due
to
reflux,
primarily
affecting
left
side.
It
affects
15%
men
a
prevalent
contributor
male
infertility.
complex
disorder
influenced
by
genetic,
epigenetic,
environmental
factors.
Epigenetic
modifications,
which
regulate
genome
activity
independently
DNA
or
RNA
sequences,
may
contribute
development
severity
varicocele.
These
include
methylation,
histone
modifications
like
N6-methyladenosine
(m6A).
Irregularities
m6A-RNA
methylation
during
spermatogenesis
can
cause
gene
expression
abnormalities,
damage,
decreased
fertility
varicocele
patients.
OBJECTIVE
AND
RATIONALE
The
review
aims
comprehensively
understand
underlying
mechanisms
varicocele,
condition
that
significantly
impact
fertility.
By
exploring
role
specifically
synthesize
evidence
from
basic,
preclinical,
clinical
research
expand
existing
knowledge
on
this
subject.
ultimate
goal
identify
potential
avenues
for
developing
targeted
treatments
effectively
improve
ultimately
increase
sperm
quality
affected
individuals.
SEARCH
METHODS
A
thorough
investigation
scientific
literature
was
conducted
through
searches
PubMed,
Google
Scholar,
Science
Direct
databases
until
May
2024.
All
studies
investigating
relationship
between
infertility,
particularly
were
reviewed,
most
pertinent
reports
included.
Keywords
such
as
epigenetics,
hypermethylation,
hypomethylation,
spermatozoa,
semen
parameters,
spermatogenesis,
infertility
used
search,
either
individually
combination.
OUTCOMES
has
specialized
morphology
essential
successful
fertilization,
its
epigenome
unique,
potentially
playing
key
embryogenesis.
Sperm
major
epigenetic
marks,
testicular
genes
crucial
normal
spermatogenesis.
This
explores
responding
oxidative
stress
how
various
nutrients
influence
their
function
condition.
Evidence
suggests
link
aberrant
DNA/m6A-RNA
patterns,
especially
but
body
still
limited.
Further
are
needed
regulators
expression.
Thus,
analyzing
5mC/5hmC
levels
reveal
defects
predict
reproductive
outcomes.
WIDER
IMPLICATIONS
Nutri-epigenomics
emerging
field
could
enhance
management
diseases
with
unpredictable
risks
consequences,
even
among
individuals
similar
lifestyles,
elucidating
nutrition
one-carbon
metabolism.
However,
importance
metabolism
not
well-recognized.
Health
status
diet
associated
modification.
Future
should
optimal
patterns
promote
health
investigate
modulating
achieve
this.
Furthermore,
additional
necessary
develop
personalized
dietary
strategies
longitudinal
research.
gap
exists
interventions
utilizing
epigenetics
therapeutic
method
treating
REGISTRATION
NUMBER
Not
applicable.
Язык: Английский
Associations between dietary one-carbon metabolism nutrients, genetic risk, with Alzheimer's disease: a prospective cohort study
American Journal of Clinical Nutrition,
Год журнала:
2024,
Номер
120(5), С. 1009 - 1018
Опубликована: Авг. 30, 2024
Язык: Английский
The Pivotal Role of One-Carbon Metabolism in Neoplastic Progression During the Aging Process
Biomolecules,
Год журнала:
2024,
Номер
14(11), С. 1387 - 1387
Опубликована: Окт. 31, 2024
One-carbon
(1C)
metabolism
is
a
complex
network
of
metabolic
reactions
closely
related
to
producing
1C
units
(as
methyl
groups)
and
utilizing
them
for
different
anabolic
processes,
including
nucleotide
synthesis,
methylation,
protein
reductive
metabolism.
These
pathways
support
the
high
proliferative
rate
cancer
cells.
While
drugs
that
target
(like
methotrexate)
have
been
used
treatment,
they
often
significant
side
effects.
Therefore,
developing
new
with
minimal
effects
necessary
effective
treatment.
Methionine,
glycine,
serine
are
main
three
precursors
vital
not
only
cells
but
also
non-proliferative
in
regulating
energy
homeostasis
aging
process.
Understanding
potential
role
crucial
advancing
our
knowledge
neoplastic
progression.
This
review
provides
comprehensive
understanding
molecular
complexities
context
aging,
paving
way
researchers
explore
avenues
advanced
therapeutic
interventions
cancer.
Язык: Английский