Annals of Human Genetics,
Год журнала:
2023,
Номер
88(1), С. 27 - 44
Опубликована: Июль 10, 2023
SUMMARY
Primary
cilia
play
critical
roles
in
regulating
signaling
pathways
that
underlie
several
developmental
processes.
In
the
nervous
system,
are
known
to
regulate
signals
guide
neuron
development.
Cilia
dysregulation
is
implicated
neurological
diseases,
and
underlying
mechanisms
remain
poorly
understood.
research
has
predominantly
focused
on
neurons
overlooked
diverse
population
of
glial
cells
brain.
Glial
essential
during
neurodevelopment,
their
dysfunction
contributes
disease;
however,
relationship
between
function
development
understudied.
Here
we
review
state
field
highlight
cell
types
where
found
ciliary
functions
linked
This
work
uncovers
importance
raises
outstanding
questions
for
field.
We
poised
make
progress
understanding
human
contribution
diseases.
Cell,
Год журнала:
2024,
Номер
187(11), С. 2601 - 2627
Опубликована: Май 1, 2024
Mitochondria
reside
at
the
crossroads
of
catabolic
and
anabolic
metabolism—the
essence
life.
How
their
structure
function
are
dynamically
tuned
in
response
to
tissue-specific
needs
for
energy,
growth
repair,
renewal
is
being
increasingly
understood.
respond
intrinsic
extrinsic
stresses
can
alter
cell
organismal
by
inducing
metabolic
signaling
within
cells
distal
tissues.
Here,
we
review
how
centrality
mitochondrial
functions
manifests
health
a
broad
spectrum
diseases
aging.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Июль 24, 2024
Neuroglia
critically
shape
the
brain´s
response
to
ischemic
stroke.
However,
their
phenotypic
heterogeneity
impedes
a
holistic
understanding
of
cellular
composition
early
lesion.
Here
we
present
single
cell
resolution
transcriptomics
dataset
acute
infarction.
Oligodendrocyte
lineage
cells
and
astrocytes
range
among
most
transcriptionally
perturbed
populations
exhibit
infarction-
subtype-specific
molecular
signatures.
Specifically,
find
infarction
restricted
proliferating
oligodendrocyte
precursor
(OPCs),
mature
oligodendrocytes
reactive
astrocytes,
exhibiting
transcriptional
commonalities
in
injury.
OPCs
are
involved
shared
immuno-glial
cross
talk
with
stroke-specific
myeloid
cells.
Within
perilesional
zone,
osteopontin
positive
accumulate
close
proximity
CD44
Nature Metabolism,
Год журнала:
2023,
Номер
5(3), С. 385 - 397
Опубликована: Март 6, 2023
Abstract
Depriving
cells
of
nutrients
triggers
an
energetic
crisis,
which
is
resolved
by
metabolic
rewiring
and
organelle
reorganization.
Primary
cilia
are
microtubule-based
organelles
at
the
cell
surface,
capable
integrating
multiple
signalling
cues,
but
their
precise
sensory
function
not
fully
understood.
Here
we
show
that
primary
respond
to
nutrient
availability
adjust
length
via
glutamine-mediated
anaplerosis
facilitated
asparagine
synthetase
(ASNS).
Nutrient
deprivation
causes
elongation,
mediated
reduced
mitochondrial
function,
ATP
AMPK
activation
independently
mTORC1.
Of
note,
glutamine
removal
replenishment
necessary
sufficient
induce
ciliary
elongation
or
retraction,
respectively,
under
stress
conditions
both
in
vivo
vitro
restoring
ASNS-dependent
glutamate
generation.
Ift88-mutant
lacking
glutamine-dependent
during
stress,
due
expression
activity
ASNS
base
cilia.
Our
data
indicate
a
role
for
responding
to,
possibly
sensing,
cellular
levels
stress.
Nature Neuroscience,
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 5, 2024
Multiple
sclerosis
(MS)
is
a
chronic
inflammatory
disease
of
the
central
nervous
system.
Inflammation
gradually
compartmentalized
and
restricted
to
specific
tissue
niches
such
as
lesion
rim.
However,
precise
cell
type
composition
niches,
their
interactions
changes
between
active
inactive
stages
are
incompletely
understood.
We
used
single-nucleus
spatial
transcriptomics
from
subcortical
MS
corresponding
control
tissues
map
types
associated
pathways
nonlesion
areas.
identified
perivascular
spaces,
inflamed
rim
or
core
that
with
glial
scar
cilia-forming
astrocyte
subtype.
Focusing
on
lesions,
we
uncovered
cell–cell
communication
events
myeloid,
endothelial
types.
Our
results
provide
insight
into
cellular
composition,
multicellular
programs
intercellular
in
along
conversion
homeostatic
dysfunctional
state
underlying
progression
MS.
Lerma-Martin
et
al.
generated
paired
RNA
sequencing
dataset
multiple
identifying
key
driving
inflammation
at
The Journal of Physiology,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 18, 2025
Abstract
Mitochondria
play
essential
metabolic
roles
and
are
increasingly
understood
to
interact
with
other
organelles,
influencing
cellular
function
disease.
Primary
cilia,
as
sensory
signalling
crucial
for
neuronal
communication
function.
Emerging
evidence
suggests
that
mitochondria
primary
cilia
may
regulate
processes,
recently
shown
in
brain
cells
such
astrocytes.
Here,
we
investigated
whether
also
neurons,
focusing
on
molecular
pathways
linking
both
organelles
structural
components
within
cilia.
We
employed
a
cross‐species,
pathway‐focused
approach
explore
connections
between
mitochondrial
ciliary
revealing
strong
associations
suggesting
coordinated
functionality.
Furthermore,
found
viral‐induced
downregulation
of
the
fusion
gene
mitofusin
2
(
Mfn2
)
dopamine
D1
receptor‐expressing
medium
spiny
neurons
(D1‐MSNs)
nucleus
accumbens
(NAc)
altered
expression,
Crocc
–
encoding
rootletin
showing
most
pronounced
downregulation.
This
reduction
expression
was
linked
decreased
levels
protein,
key
component
rootlet.
Notably,
viral‐mediated
overexpression
restored
complexity
elongation,
without
compromising
adaptation
Our
findings
provide
novel
functional
mitochondria–cilia
interaction
specifically
striatal
D1‐MSNs.
These
results
reveal
previously
unrecognized
role
dynamics
regulating
structure
potential
implications
neuropsychiatric
neurodegenerative
disease
mechanisms.
image
Key
points
cell
structures
known
producing
energy
but
emerging
regulators
components,
including
antenna‐like
involved
communication.
Previous
studies
suggest
influence
function,
However,
this
has
not
been
explored
neurons.
study
shows
natural
variation
correlates
rats
mice.
Reducing
(Mfn2),
protein
mitochondria–endoplasmic
reticulum
interactions,
changes
specific
pathways,
notably
Crocc,
structure,
reduces
its
product,
rootletin,
which
supports
integrity.
an
important
highlighting
pathway
regulation
signalling.
The Journal of Cell Biology,
Год журнала:
2024,
Номер
223(9)
Опубликована: Май 20, 2024
Ciliopathies
are
often
caused
by
defects
in
the
ciliary
microtubule
core.
Glutamylation
is
abundant
cilia,
and
its
dysregulation
may
contribute
to
ciliopathies
neurodegeneration.
Mutation
of
deglutamylase
CCP1
causes
infantile-onset
In
C.
elegans,
ccpp-1
loss
age-related
degradation
that
suppressed
a
mutation
conserved
NEK10
homolog
nekl-4.
NEKL-4
absent
from
yet
it
negatively
regulates
stability
via
an
unknown,
glutamylation-independent
mechanism.
We
show
was
mitochondria-associated.
Additionally,
nekl-4
mutants
had
longer
mitochondria,
higher
baseline
mitochondrial
oxidation
state,
ccpp-1∆
mutant
lifespan
extension
response
oxidative
stress.
A
kinase-dead
nekl-4(KD)
ectopically
localized
cilia
rescued
degenerating
doublet
B-tubules.
nondegradable
nekl-4(PEST∆)
resembled
with
dye-filling
B-tubule
breaks.
The
Dyf
phenotype
depolymerizing
kinesin-8
KLP-13/KIF19A.
conclude
influences
activating
kinesins
promoting
homeostasis.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2022,
Номер
unknown
Опубликована: Апрель 9, 2022
Abstract
The
lack
of
understanding
the
cellular
and
molecular
basis
clinical
genetic
heterogeneity
in
progressive
multiple
sclerosis
(MS)
has
hindered
search
for
new
effective
therapies.
Here,
to
address
this
gap,
we
analysed
632,000
single
nuclei
RNAseq
profiles
156
brain
tissue
samples,
comprising
white
matter
(WM)
lesions,
normal
appearing
WM,
grey
(GM)
lesions
GM
from
54
MS
patients
26
controls.
We
observed
expected
changes
overall
neuronal
glial
numbers
previously
described
within
classical
lesion
subtypes.
found
highly
cell
type-specific
gene
expression
tissue,
with
distinct
differences
between
WM
areas,
confirming
different
pathologies.
However,
surprisingly,
did
not
observe
signatures
types,
rather
a
continuum
change.
This
indicates
that
characterization
better
reflects
abundance
than
type
expression,
global
disease
effect.
Furthermore,
major
biological
determinants
variability
samples
relate
individual
patient
effects,
types
or
other
metadata.
identify
four
subgroups
patterns
oligodendrocyte
stress
and/or
maturation,
suggestive
engagement
pathological
processes,
an
additional
more
variable
regenerative
astrocyte
signature.
discovery
these
patterns,
which
were
also
independent
cohort,
provides
framework
use
biomarkers
stratify
optimal
therapeutic
approaches
MS,
significantly
advances
our
mechanistic
highlights
need
precision-medicine
among
patients.
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(19), С. 14421 - 14421
Опубликована: Сен. 22, 2023
Neurodegeneration
is
an
age-dependent
progressive
phenomenon
with
no
defined
cause.
Aging
the
main
risk
factor
for
neurodegenerative
diseases.
During
aging,
activated
microglia
undergo
phenotypic
alterations
that
can
lead
to
neuroinflammation,
which
a
well-accepted
event
in
pathogenesis
of
Several
common
mechanisms
are
shared
by
genetically
or
pathologically
distinct
diseases,
such
as
excitotoxicity,
mitochondrial
deficits
and
oxidative
stress,
protein
misfolding
translational
dysfunction,
autophagy
activation.
Progressive
loss
neuronal
population
due
increased
stress
leads
mostly
accumulation
dysfunctional
mitochondria.
Mitochondrial
dysfunction
excessive
neuroinflammatory
responses
both
sufficient
induce
pathology
neurodegeneration.
Therefore,
quality
control
key
determinant
health
survival
cells
brain.
Research
has
been
primarily
focused
demonstrate
significance
health,
despite
important
contributions
non-neuronal
constitute
significant
portion
brain
volume.
Moreover,
morphology
function
distinctly
diverse
different
tissues;
however,
little
known
about
their
molecular
diversity
among
cell
types.
dynamics
types
markedly
decide
fate
overall
health;
therefore,
it
not
justifiable
overlook
active
contribution
facilitating
health.
In
this
review
article,
we
aim
discuss
how
remarkable
highly
synchronized
connecting
property
keeping
neurons
healthy