bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Nov. 17, 2023
Summary
Tauopathies
are
neurodegenerative
disorders
in
which
the
pathological
intracellular
aggregation
of
protein
tau
causes
cognitive
deficits.
Additionally,
clinical
studies
report
muscle
weakness
populations
with
tauopathy.
However,
whether
neuronal
species
confer
weakness,
and
skeletal
maintains
contractile
capacity
primary
tauopathy
remains
unknown.
Here,
we
identified
abnormalities
a
mouse
model
tauopathy,
expressing
human
mutant
P301L-tau
using
adeno-associated
virus
serotype
8
(AAV8).
AAV8-P301L
mice
showed
grip
strength
deficits,
hyperactivity,
abnormal
histological
features
muscle.
spatially
resolved
gene
expression
cross
sections
were
altered
myofibers.
Transcriptional
changes
alterations
genes
encoding
sarcomeric
proteins,
proposing
phenotype.
Strikingly,
specific
force
soleus
was
blunted
male
mice.
Our
findings
suggest
has
peripheral
consequences
that
contribute
to
PLoS Biology,
Journal Year:
2025,
Volume and Issue:
23(1), P. e3002998 - e3002998
Published: Jan. 29, 2025
Ubiquitin-conjugating
enzymes
(E2s)
are
key
for
protein
turnover
and
quality
control
via
ubiquitination.
Some
E2s
also
physically
interact
with
the
proteasome,
but
it
remains
undetermined
which
maintain
proteostasis
during
aging.
Here,
we
find
that
have
diverse
roles
in
handling
a
model
aggregation-prone
(huntingtin-polyQ)
Drosophila
retina:
while
some
mediate
aggregate
assembly,
UBE2D/effete
(eff)
other
required
huntingtin-polyQ
degradation.
UBE2D/eff
is
skeletal
muscle:
eff
levels
decline
aging,
muscle-specific
knockdown
causes
an
accelerated
buildup
insoluble
poly-ubiquitinated
proteins
(which
progressively
accumulate
aging)
shortens
lifespan.
Mechanistically,
necessary
to
optimal
proteasome
function:
reduces
proteolytic
activity
of
this
rescued
by
transgenic
expression
human
UBE2D2,
homolog.
Likewise,
UBE2D2
partially
rescues
lifespan
deficits
caused
RNAi
re-establishes
physiological
-regulated
proteins.
Interestingly,
young
age
reproduces
part
proteomic
changes
normally
occur
old
muscles,
suggesting
decrease
occurs
aging
contributes
reshaping
composition
muscle
proteome.
However,
concertedly
up-regulated
regulators
(e.g.,
chaperones
Pomp)
transcriptionally
induced
presumably
as
adaptive
stress
response
loss
proteostasis.
Altogether,
these
findings
indicate
E2
ubiquitin-conjugating
enzyme
ensures
helps
youthful
proteome
Cell Proliferation,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 24, 2025
ABSTRACT
Ageing
is
often
accompanied
by
cognitive
decline
and
an
increased
risk
of
dementia.
Exercise
a
powerful
tool
for
slowing
brain
ageing
enhancing
function,
as
well
alleviating
depression,
improving
sleep,
promoting
overall
well‐being.
The
connection
between
exercise
healthy
particularly
intriguing,
with
exercise‐induced
pathways
playing
key
roles.
This
review
explores
the
link
health,
focusing
on
how
skeletal
muscle
influences
through
muscle–brain
crosstalk.
We
examine
interaction
well‐known
myokines,
including
brain‐derived
neurotrophic
factor,
macrophage
colony‐stimulating
vascular
endothelial
growth
factor
cathepsin
B.
Neuroinflammation
accumulates
in
leads
to
decline,
impaired
motor
skills
susceptibility
neurodegenerative
diseases.
Finally,
we
evidence
effects
neuronal
myelination
central
nervous
system,
crucial
maintaining
health
throughout
lifespan.
Experimental Neurology,
Journal Year:
2024,
Volume and Issue:
376, P. 114757 - 114757
Published: March 18, 2024
The
intricate
functional
interactions
between
mitochondria
and
lysosomes
play
a
pivotal
role
in
maintaining
cellular
homeostasis
proper
functions.
This
dynamic
interplay
involves
the
exchange
of
molecules
signaling,
impacting
metabolism,
mitophagy,
organellar
dynamics,
responses
to
stress.
Dysregulation
these
processes
has
been
implicated
various
neurodegenerative
diseases.
Additionally,
mitochondrial-lysosomal
crosstalk
regulates
exosome
release
neurons
glial
cells.
Under
stress
conditions,
cells
exhibit
mitochondrial
dysfunction
fragmented
network,
which
further
leads
lysosomal
dysfunction,
thereby
inhibiting
autophagic
flux
enhancing
release.
comprehensive
review
synthesizes
current
knowledge
on
regulation
cell
death,
organelle
vesicle
trafficking,
emphasizing
their
significant
contributions
Furthermore,
we
explore
emerging
field
nanomedicine
management
provides
readers
with
an
insightful
overview
nano
strategies
that
are
currently
advancing
mitochondrial-lysosome-extracellular
axis
as
therapeutic
approach
for
mitigating
medRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: April 24, 2024
ABSTRACT
Accurate
differential
diagnosis
of
dementia
disorders
including
Alzheimer’s
disease
(AD),
frontotemporal
(FTD),
with
Lewy
bodies
(DLB),
Parkinson’s
(PDD),
and
vascular
cognitive
impairment
(VCID),
along
conditions
like
prodromal
mild
(MCI)
or
negative
controls
(NCs),
continues
to
challenge
neurologists.
The
nuanced
sometimes
shared
pathophysiological
features
underscore
the
need
for
precision
in
developing
disease-modifying
therapies.
In
pursuit
reliable
antemortem
biomarkers,
extracellular
vesicles
(EVs)
have
emerged
as
a
popular
tool
their
capacity
encapsulate
disease-specific
signatures,
particularly
neurodegenerative
neurological
disorders.
To
this
end,
we
performed
comprehensive,
PRISMA-guided
systematic
review
meta-analysis,
utilizing
sophisticated
statistical
modeling
determine
diagnostic
accuracy,
explore
between-study
variance
heterogeneity
(I
2
),
investigate
potential
publication
bias
using
various
tests.
Biomarkers
derived
from
general
EVs
demonstrated
superior
less
variance,
heterogeneity,
than
those
speculative
CNS-enriched
EVs.
trim-and-fill
method
suggested
overestimation
effectiveness
biomarkers
due
four
hypothesized
missing
studies
low
results,
but
none
Meta-regressions
revealed
that
cerebrospinal
fluid
serum,
involving
non-fasting
individuals,
sampling
afternoon,
employing
citrate
instead
EDTA
blood
collection,
thrombin
coagulation
factor
depletion,
isolating
purer
methods
such
combined
ultracentrifugation
size-exclusion
chromatography,
not
freezing
post-isolation,
quantifying
miRNA
achieved
better
accuracy
heterogeneity.
was
differentiating
among
different
However,
analysis
diagnosing
persons
AD
vs.
VCID
highest
suggesting
further
may
focus
on
comparison.
Additionally,
highlight
several
limitations
included
recommend
following:
Implement
use
appropriate
controls,
thorough
documentation
preanalytical
factors,
inclusion
more
groups
beyond
AD,
comprehensive
reporting
pharmacological
treatments,
consideration
racial
ethnic
minority
groups,
adherence
ISEV
guidelines,
application
A-T-N
framework,
detailed
stages,
extension
diagnosis,
reanalysis
when
postmortem
definitive
diagnostics
become
available,
evaluation
conversion
rates,
commitment
accurate
data
transparency.
We
hope
lessons
learned
meta-analysis
can
be
beneficial
attempting
discover
related
dementias
through
alternative
approaches.
Aging Brain,
Journal Year:
2024,
Volume and Issue:
5, P. 100110 - 100110
Published: Jan. 1, 2024
Tauopathies
are
neurodegenerative
disorders
in
which
the
pathological
intracellular
aggregation
of
protein
tau
causes
cognitive
deficits.
Additionally,
clinical
studies
report
muscle
weakness
populations
with
tauopathy.
However,
whether
neuronal
species
confer
weakness,
and
skeletal
maintains
contractile
capacity
primary
tauopathy
remains
unknown.
Here,
we
identified
abnormalities
a
mouse
model
tauopathy,
expressing
human
mutant
P301L-tau
using
adeno-associated
virus
serotype
8
(AAV8).
AAV8-P301L
mice
showed
grip
strength
deficits,
hyperactivity,
abnormal
histological
features
muscle.
spatially
resolved
gene
expression
cross
sections
were
altered
myofibers.
Transcriptional
changes
alterations
genes
encoding
sarcomeric
proteins,
proposing
phenotype.
Strikingly,
specific
force
soleus
was
blunted
male
mice.
Our
findings
suggest
has
peripheral
consequences
that
contribute
to
