Cells,
Год журнала:
2021,
Номер
10(5), С. 1078 - 1078
Опубликована: Май 1, 2021
Axons
in
the
adult
mammalian
nervous
system
can
extend
over
formidable
distances,
up
to
one
meter
or
more
humans.
During
development,
axonal
and
dendritic
growth
requires
continuous
addition
of
new
membrane.
Of
three
major
kinds
membrane
lipids,
phospholipids
are
most
abundant
all
cell
membranes,
including
neurons.
Not
only
immature
axons,
but
also
severed
axons
require
large
amounts
lipids
for
axon
regeneration
occur.
Lipids
serve
as
energy
storage,
signaling
molecules
they
contribute
tissue
physiology,
demonstrated
by
a
variety
metabolic
disorders
which
harmful
accumulate
various
tissues
through
body.
Detrimental
changes
lipid
metabolism
excess
accumulation
lack
regeneration,
poor
neurological
outcome
complications
after
central
(CNS)
trauma
brain
spinal
cord
injury.
Recent
evidence
indicates
that
rewiring
be
manipulated
therapeutic
gain,
it
favors
conditions
CNS
repair.
Here,
we
review
role
ectopic
growth,
In
addition,
outline
molecular
pharmacological
strategies
fine-tune
composition
neurons
non-neuronal
cells
exploited
improve
recovery
disease.
Cells,
Год журнала:
2020,
Номер
9(1), С. 150 - 150
Опубликована: Янв. 8, 2020
Mitochondrial
dysfunction
is
a
central
aspect
of
aging
and
neurodegenerative
diseases,
including
Alzheimer’s
disease,
Parkinson’s
amyotrophic
lateral
sclerosis,
Huntington’s
disease.
Mitochondria
are
the
main
cellular
energy
powerhouses,
supplying
most
ATP
by
oxidative
phosphorylation,
which
required
to
fuel
essential
neuronal
functions.
Efficient
removal
aged
dysfunctional
mitochondria
through
mitophagy,
cargo-selective
autophagy,
crucial
for
mitochondrial
maintenance
health.
Mechanistic
studies
into
mitophagy
have
highlighted
an
integrated
elaborate
network
that
can
regulate
turnover.
In
this
review,
we
provide
updated
overview
recent
discoveries
advancements
on
pathways
discuss
molecular
mechanisms
underlying
defects
in
disease
other
age-related
as
well
therapeutic
potential
mitophagy-enhancing
strategies
combat
these
disorders.
Biomedicine & Pharmacotherapy,
Год журнала:
2022,
Номер
148, С. 112681 - 112681
Опубликована: Фев. 14, 2022
Alzheimer's
disease
(AD)
is
the
most
common
neurodegenerative
disease,
with
cognitive
decline
as
primary
clinical
feature.
According
to
epidemiological
statistics,
50
million
people
worldwide
are
currently
affected
by
disease.
Although
new
drugs
such
aducanumab
have
been
approved
for
use
in
treatment
of
AD,
none
them
reversed
progression
AD.
MicroRNAs
(miRNAs)
small
molecule
RNAs
that
exert
their
biological
functions
regulating
expression
intracellular
proteins,
and
differential
abundance
varieties
found
between
central
peripheral
tissues
AD
patients
healthy
controls.
This
article
will
summarise
changes
miRNAs
process,
potential
role
diagnostic
markers
therapeutic
targets
be
explored.
Journal of Human Genetics,
Год журнала:
2022,
Номер
68(3), С. 131 - 152
Опубликована: Июнь 13, 2022
Abstract
Amyotrophic
lateral
sclerosis
(ALS)
is
an
intractable
disease
that
causes
respiratory
failure
leading
to
mortality.
The
main
locus
of
ALS
motor
neurons.
success
antisense
oligonucleotide
(ASO)
therapy
in
spinal
muscular
atrophy
(SMA),
a
neuron
disease,
has
triggered
paradigm
shift
developing
therapies.
causative
genes
and
disease-modifying
genes,
including
those
sporadic
ALS,
have
been
identified
one
after
another.
Thus,
the
freedom
target
choice
for
gene
expanded
by
ASO
strategy,
new
avenues
therapeutic
development.
Tofersen
superoxide
dismutase
1
(SOD1)
was
pioneer
ALS.
Improving
protocols
devising
early
interventions
are
vital.
In
this
review,
we
updated
knowledge
We
summarized
genetic
mutations
familial
their
clinical
features,
focusing
on
SOD1
,
fused
sarcoma
(FUS)
transacting
response
DNA-binding
protein.
frequency
C9ORF72
mutation
low
Japan,
unlike
Europe
United
States,
while
FUS
more
common,
indicating
vary
ethnicity.
A
genome-wide
association
study
revealed
which
could
be
novel
therapy.
current
status
prospects
development
were
discussed,
ethical
issues.
Furthermore,
discussed
potential
axonal
pathology
as
targets
from
perspective
intervention,
intra-axonal
transcription
factors,
neuromuscular
junction
disconnection,
dysregulated
local
translation,
abnormal
protein
degradation,
mitochondrial
pathology,
impaired
transport,
aberrant
cytoskeleton,
axon
branching.
simultaneously
discuss
important
pathological
states
cell
bodies:
persistent
stress
granules,
disrupted
nucleocytoplasmic
cryptic
splicing.
based
elucidation
intervention
molecular
expected
become
strategy
Molecular Aspects of Medicine,
Год журнала:
2023,
Номер
92, С. 101193 - 101193
Опубликована: Июнь 16, 2023
Glaucoma
is
a
common,
complex,
multifactorial
neurodegenerative
disease
characterized
by
progressive
dysfunction
and
then
loss
of
retinal
ganglion
cells,
the
output
neurons
retina.
most
common
cause
irreversible
blindness
affects
∼80
million
people
worldwide
with
many
more
undiagnosed.
The
major
risk
factors
for
glaucoma
are
genetics,
age,
elevated
intraocular
pressure.
Current
strategies
only
target
pressure
management
do
not
directly
processes
occurring
at
level
cell.
Despite
to
manage
pressure,
as
40%
patients
progress
in
least
one
eye
during
their
lifetime.
As
such,
neuroprotective
that
cell
these
great
therapeutic
need.
This
review
will
cover
recent
advances
from
basic
biology
on-going
clinical
trials
neuroprotection
covering
degenerative
mechanisms,
metabolism,
insulin
signaling,
mTOR,
axon
transport,
apoptosis,
autophagy,
neuroinflammation.
With
an
increased
understanding
both
mechanisms
disease,
we
closer
than
ever
strategy
glaucoma.
Molecular Neurodegeneration,
Год журнала:
2023,
Номер
18(1)
Опубликована: Июль 20, 2023
Abstract
Human
studies
consistently
identify
bioenergetic
maladaptations
in
brains
upon
aging
and
neurodegenerative
disorders
of
(NDAs),
such
as
Alzheimer’s
disease,
Parkinson’s
Huntington’s
Amyotrophic
lateral
sclerosis.
Glucose
is
the
major
brain
fuel
glucose
hypometabolism
has
been
observed
regions
vulnerable
to
NDAs.
Many
susceptible
are
topological
central
hub
connectome,
linked
by
densely
interconnected
long-range
axons.
Axons,
key
components
have
high
metabolic
needs
support
neurotransmission
other
essential
activities.
Long-range
axons
particularly
injury,
neurotoxin
exposure,
protein
stress,
lysosomal
dysfunction,
etc.
Axonopathy
often
an
early
sign
neurodegeneration.
Recent
ascribe
axonal
maintenance
failures
local
dysregulation.
With
this
review,
we
aim
stimulate
research
exploring
metabolically
oriented
neuroprotection
strategies
enhance
or
normalize
bioenergetics
NDA
models.
Here
start
summarizing
evidence
from
human
patients
animal
models
reveal
correlation
between
connectomic
disintegration
aging/NDAs.
To
encourage
mechanistic
investigations
on
how
dysregulation
occurs
during
aging/NDAs,
first
review
current
literature
distinct
subdomains:
axon
initial
segments,
myelinated
arbors
harboring
pre-synaptic
boutons.
In
each
subdomain,
focus
organization,
activity-dependent
regulation
system,
external
glial
support.
Second,
mechanisms
regulating
nicotinamide
adenine
dinucleotide
(NAD
+
)
homeostasis,
molecule
for
energy
metabolism
processes,
including
NAD
biosynthetic,
recycling,
consuming
pathways.
Third,
highlight
innate
vulnerability
connectome
discuss
its
perturbation
As
deficits
developing
into
NDAs,
especially
asymptomatic
phase,
they
likely
exaggerated
further
impaired
energetic
cost
neural
network
hyperactivity,
pathology.
Future
interrogating
causal
relationship
vulnerability,
axonopathy,
amyloid/tau
pathology,
cognitive
decline
will
provide
fundamental
knowledge
therapeutic
interventions.
Neurons
are
highly
polarised,
complex
and
incredibly
energy
intensive
cells,
their
demand
for
ATP
during
neuronal
transmission
is
primarily
met
by
oxidative
phosphorylation
mitochondria.
Thus,
maintaining
the
health
efficient
function
of
mitochondria
vital
integrity,
viability
synaptic
activity.
Mitochondria
do
not
exist
in
isolation,
but
constantly
undergo
cycles
fusion
fission,
actively
transported
around
neuron
to
sites
high
demand.
Intriguingly,
axonal
dendritic
exhibit
different
morphologies.
In
axons
small
sparse
whereas
dendrites
they
larger
more
densely
packed.
The
transport
mechanisms
mitochondrial
dynamics
that
underlie
these
differences,
functional
implications,
have
been
focus
concerted
investigation.
Moreover,
it
now
clear
deficiencies
can
be
a
primary
factor
many
neurodegenerative
diseases.
Here,
we
review
role
play
function,
how
processes
support
dysfunction
implicated
disease.
Autophagy,
Год журнала:
2021,
Номер
17(12), С. 4182 - 4201
Опубликована: Март 24, 2021
Mitochondria
are
the
main
cellular
energy
powerhouses
and
supply
most
of
in
form
ATP
to
fuel
essential
neuronal
functions
through
oxidative
phosphorylation
(OXPHOS).
In
Alzheimer
disease
(AD),
metabolic
mitochondrial
disruptions
an
early
feature
preceding
any
histopathological
clinical
manifestations.
Mitochondrial
malfunction
is
also
linked
synaptic
defects
AD.
Mitophagy
serves
as
a
key
quality
control
mechanism
involving
sequestration
damaged
mitochondria
within
autophagosomes
their
subsequent
degradation
lysosomes.
However,
it
remains
largely
unknown
whether
mitophagy
involved
regulation
metabolism
neurons,
if
so,
deficiency
AD
attributed
dysfunction.
Here
we
reveal
that
broadly
activated
metabolically
enhanced
neurons
upon
OXPHOS
stimulation,
which
sustains
high
energetic
activity
by
increasing
turnover
hence
facilitating
maintenance.
Unexpectedly,
AD-related
mutant
HsAPP
Tg
mouse
brains,
stimulation
fails
correct
deficits
but
exacerbates
synapse
loss
consequence
failure.
Excitingly,
lysosomal
enhancement
restores
impaired
function
promoting
elimination
mitochondria,
protecting
against
damage
brains.
Taken
together,
propose
new
controls
bioenergetic
status
furthering
our
understanding
direct
impact
on
AD-linked
shedding
light
development
novel
therapeutic
strategies
treat
combined
with
elevation
proteolytic
activity.Abbreviations:
AD:
disease;
Aβ:
amyloid-β;
APP:
amyloid
beta
precursor
protein;
AV:
autophagic
vacuole;
CHX:
cycloheximide;
CYCS:
cytochrome
c,
somatic;
DIV:
days
vitro;
FRET:
Förster
resonance
transfer;
Gln,
glutamine;
LAMP1:
associated
membrane
protein
1;
LE:
late
endosome;
Mito:
mitochondria;
Δψm:
potential;
OCR:
oxygen
consumption
rate;
OXPHOS:
phosphorylation;
SQSTM1/p62:
sequestosome
RHEB:
Ras
homolog,
mTORC1
binding;
ROS:
reactive
species;
STX1:
syntaxin
SYP:
synaptophysin;
Tg:
transgenic;
TMRE:
tetramethylrhodamine
ethyl
ester;
TEM:
transmission
electron
microscopy;
WT:
wild
type.