Genes,
Год журнала:
2024,
Номер
15(12), С. 1599 - 1599
Опубликована: Дек. 14, 2024
Background/Objectives:
Aging
is
a
natural
physiological
process
involving
biological
and
genetic
pathways.
Growing
evidence
suggests
that
alterations
in
the
epigenome
during
aging
result
transcriptional
changes,
which
play
significant
role
onset
of
age-related
diseases,
including
cancer,
cardiovascular
disease,
diabetes,
neurodegenerative
disorders.
For
this
reason,
epigenetic
diseases
have
been
reviewed,
major
extrinsic
factors
influencing
these
identified.
In
addition,
gut
microbiome
its
metabolites
as
modifiers
has
addressed.
Results:
Long-term
exposure
to
such
air
pollution,
diet,
drug
use,
environmental
chemicals,
microbial
infections,
physical
activity,
radiation,
stress
provoke
changes
host
through
several
endocrine
immune
pathways,
potentially
accelerating
process.
Diverse
studies
reported
plays
critical
regulating
brain
cell
functions
DNA
methylation
histone
modifications.
The
interaction
between
genes
serves
source
adaptive
variation,
contributing
phenotypic
plasticity.
However,
molecular
mechanisms
signaling
pathways
driving
are
still
not
fully
understood.
Conclusions:
Extrinsic
potential
inducers
alterations,
may
important
implications
for
longevity.
an
effector
gene
expression
modifications,
while
bidirectional
interactions
with
underexplored
roles
non-bacterial
microorganisms
fungi
viruses
highlight
need
further
research.
Journal of Clinical Investigation,
Год журнала:
2023,
Номер
133(13)
Опубликована: Июль 2, 2023
Solid-like
protein
deposits
found
in
aged
and
diseased
human
brains
have
revealed
a
relationship
between
insoluble
accumulations
the
resulting
deficits
neurologic
function.
Clinically
diverse
neurodegenerative
diseases,
including
Alzheimer's
disease,
Parkinson's
frontotemporal
lobar
degeneration,
amyotrophic
lateral
sclerosis,
exhibit
unique
disease-specific
biochemical
signatures
abnormal
depositions
that
often
correlate
with
disease
pathogenesis.
Recent
evidence
indicates
many
pathologic
proteins
assemble
into
liquid-like
phases
through
highly
coordinated
process
of
liquid-liquid
phase
separation.
Over
last
decade,
biomolecular
transitions
emerged
as
fundamental
mechanism
cellular
organization.
Liquid-like
condensates
organize
functionally
related
biomolecules
within
cell,
neuropathology-associated
reside
these
dynamic
structures.
Thus,
examining
enhances
our
understanding
molecular
mechanisms
mediating
toxicity
across
diseases.
This
Review
explores
known
contributing
to
aberrant
focusing
on
tau
TDP-43
proteinopathies
outlining
potential
therapeutic
strategies
regulate
events.
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Янв. 18, 2025
Hereditary
spastic
paraplegia
(HSP)
encompasses
a
group
of
rare
genetic
diseases
primarily
affecting
motor
neurons.
Among
these,
type
11
(SPG11)
represents
complex
form
HSP
caused
by
deleterious
variants
in
the
SPG11
gene,
which
encodes
spatacsin
protein.
Previous
studies
have
described
several
potential
roles
for
spatacsin,
including
its
involvement
lysosome
and
autophagy
mechanisms,
neuronal
neurites
development
or
mitochondria
function.
Despite
these
findings,
precise
function
protein
remains
elusive.
To
elucidate
function,
we
conducted
an
extensive
RNA
sequencing
(RNAseq)
experiment
transcriptomic
analysis
three
distinct
neural
structures
(cerebellum,
cortex
hippocampus)
at
different
ages
(6
weeks,
4
months
8
months)
both
wild
Spg11−/−
mice.
Our
functional
differentially
expressed
genes
(DEGs)
Gene
Set
Enrichment
Analysis
(GSEA)
revealed
dysregulation
pathways
related
to
inflammation,
metabolism
neurite
development,
factors
frequently
implicated
neurodegenerative
disorders.
Notably,
also
observed
early
deregulation
cellular
cell
proliferation.
results
represent
significant
step
towards
better
understanding
functions
underlying
mechanisms
disrupted
absence.
With
the
aging
of
global
population,
accumulating
interest
is
focused
on
manipulating
fundamental
aging-related
signaling
pathways
to
delay
physiological
process
and
eventually
slow
or
prevent
appearance
severity
multiple
diseases.
Recently,
emerging
evidence
has
shown
that
RNA
modifications,
which
were
historically
considered
infrastructural
features
cellular
RNAs,
are
dynamically
regulated
across
most
species
in
cells
thereby
critically
involved
major
biological
processes,
including
senescence
aging.
In
this
review,
we
summarize
current
knowledge
about
modifications
provide
a
catalog
different
species,
mRNAs,
miRNAs,
lncRNA,
tRNAs,
rRNAs.
Most
importantly,
focus
regulation
roles
these
diseases,
neurodegenerative
cardiovascular
cataracts,
osteoporosis,
fertility
decline.
This
would
be
an
important
step
toward
better
understanding
mechanisms
facilitating
development
novel
diagnostics
therapeutics
for
Comptes Rendus Chimie,
Год журнала:
2025,
Номер
28(G1), С. 111 - 129
Опубликована: Фев. 13, 2025
Bisubstrate
compounds
are
designed
to
mimic
the
interaction
of
enzymes
with
their
two
natural
substrates.
These
molecules
contain
moieties
mimicking
substrates
linked
together
by
a
covalent
bridge,
which
enhances
both
selectivity
and
potency.
This
review
shows
synthesis
utility
RNA
conjugates,
particularly
peptidyl–RNA
cofactor–RNA
as
bisubstrate
analogues
for
studying
major
families
transferases:
Fem
aminoacyl
transferases
involved
in
bacterial
cell
wall
m6A
methyltransferases,
catalyze
methylation.
The
synthetic
routes
developed
access
conjugates
cover
nucleoside
nucleotide
chemistry,
site-specific
modifications,
solid
phase
or
chemoenzymatic
processes
well
strategies
oligonucleotide
late-stage
functionalization.
have
been
used
not
only
inhibitors
these
but
also
valuable
chemical
tools
elucidating
enzyme
mechanisms
facilitating
structural
studies.
Les
composés
bisubstrats
sont
conçus
pour
imiter
l'interaction
entre
les
et
leurs
deux
substrats
naturels.
Ces
molécules
contiennent
fragments
qui
miment
de
l'enzyme,
liés
eux
par
un
lien
covalent,
ce
permet
d'améliorer
à
la
fois
sélectivité
puissance
des
composés.
Cette
revue
présente
synthèse
l'utilisation
conjugués
d'ARN,
en
particulier
peptidyl-ARN
cofacteur-ARN,
comme
étudier
grandes
familles
d'ARN
transférases
:
aminoacyl-transférases
impliquées
dans
paroi
cellulaire
bactérienne
méthyltransférases
catalysent
méthylation
l'ARN.
voies
développées
accéder
aux
font
appel
chimie
nucléosides
nucléotides,
réactions
chimio
spécifiques,
sur
support
solide,
processus
chimio-enzymatiques,
ou
stratégies
fonctionnalisation
tardive
oligonucléotides.
ont
été
utilisées
inhibiteurs
transférases,
mais
également
outils
chimiques
faciliter
études
structurales
élucider
mécanismes
enzymatiques.
European Journal of Neuroscience,
Год журнала:
2025,
Номер
61(8)
Опубликована: Апрель 1, 2025
ABSTRACT
Neurodegeneration
is
featured
by
the
gradual
stagnation
of
neuronal
function
and
structure,
leading
to
significant
motor
cognitive
impairments.
The
primary
histopathological
features
underlying
these
conditions
include
cumulation
pathological
protein
aggregates,
chronic
inflammation,
cell
death.
Alzheimer's
disease
(
AD
)
Parkinson's
(PD)
are
prominent
examples
neurodegenerative
diseases
(NDDs).
As
2023,
over
65
million
people
worldwide
affected
PD,
with
prevalence
steadily
increasing
time.
Interestingly,
there
no
effective
therapies
available
halt
or
slow
NDD
progression.
Most
approved
treatments
focused
on
symptom
management
often
associated
substantial
side
effects.
Given
limitations,
development
novel
therapeutic
approaches
targeting
molecular
mechanisms
disorders
essential.
Notably,
RNA‐based
therapeutics
have
recently
emerged
as
a
potential
approach
for
managing
various
neurological
diseases,
offering
innovative
interventions
in
NDD.
In
this
review,
we
discussed
pathogenic
role
aggregates
highlighted
emerging
strategies
aimed
at
proteins.
