Acta Neuropathologica,
Год журнала:
2018,
Номер
135(4), С. 489 - 509
Опубликована: Март 16, 2018
Amyotrophic
lateral
sclerosis
(ALS)
is
a
relentlessly
progressive
and
fatal
neurodegenerative
disorder
that
primarily
affects
motor
neurons.
Despite
our
increased
understanding
of
the
genetic
factors
contributing
to
ALS,
no
effective
treatment
available.
A
growing
body
evidence
shows
disturbances
in
energy
metabolism
ALS.
Moreover,
remarkable
vulnerability
neurons
ATP
depletion
has
become
increasingly
clear.
Here,
we
review
metabolic
alterations
present
ALS
patients
models,
discuss
selective
energetic
stress,
provide
an
overview
tested
emerging
approaches
treat
We
believe
further
biology
can
lead
identification
novel
therapeutic
targets.
Redox Biology,
Год журнала:
2018,
Номер
15, С. 490 - 503
Опубликована: Фев. 3, 2018
The
human
brain
consumes
20%
of
the
total
basal
oxygen
(O2)
budget
to
support
ATP
intensive
neuronal
activity.
Without
sufficient
O2
demands,
activity
fails,
such
that,
even
transient
ischemia
is
neurodegenerative.
While
essentiality
function
clear,
how
oxidative
stress
causes
neurodegeneration
ambiguous.
Ambiguity
exists
because
many
reasons
why
susceptible
remain
obscure.
Many
are
erroneously
understood
as
deleterious
result
adventitious
derived
free
radical
and
non-radical
species
generation.
To
understand
underpin
stress,
one
must
first
re-cast
in
a
positive
light
their
deliberate
generation
enables
achieve
critical
functions
(e.g.
synaptic
plasticity)
through
redox
signalling
(i.e.
functionality).
Using
radicals
derivatives
signal
sensitises
when
goes
awry
negative
advance
mechanistic
understanding,
we
rationalise
13
stress.
Key
include
inter
alia
unsaturated
lipid
enrichment,
mitochondria,
calcium,
glutamate,
modest
antioxidant
defence,
active
transition
metals
neurotransmitter
auto-oxidation.
We
review
RNA
oxidation
an
underappreciated
cause
complex
interplay
between
each
reason
dictates
susceptibility
dynamic
context
neural
identity
dependent
manner.
Our
discourse
sets
stage
for
investigators
interrogate
biochemical
basis
health
disease.
Physiological Reviews,
Год журнала:
2018,
Номер
99(1), С. 949 - 1045
Опубликована: Дек. 19, 2018
Glucose
is
the
long-established,
obligatory
fuel
for
brain
that
fulfills
many
critical
functions,
including
ATP
production,
oxidative
stress
management,
and
synthesis
of
neurotransmitters,
neuromodulators,
structural
components.
Neuronal
glucose
oxidation
exceeds
in
astrocytes,
but
both
rates
increase
direct
proportion
to
excitatory
neurotransmission;
signaling
metabolism
are
closely
coupled
at
local
level.
Exact
details
neuron-astrocyte
glutamate-glutamine
cycling
remain
be
established,
specific
roles
lactate
cellular
energetics
these
processes
debated.
Glycolysis
preferentially
upregulated
during
activation
even
though
oxygen
availability
sufficient
(aerobic
glycolysis).
Three
major
pathways,
glycolysis,
pentose
phosphate
shunt,
glycogen
turnover,
contribute
utilization
excess
oxygen,
adrenergic
regulation
aerobic
glycolysis
draws
attention
astrocytic
metabolism,
particularly
which
has
a
high
impact
on
oxygen-carbohydrate
mismatch.
Aerobic
proposed
predominant
young
children
regions,
re-evaluation
data
necessary.
Shuttling
glucose-
glycogen-derived
from
astrocytes
neurons
activation,
neurotransmission,
memory
consolidation
controversial
topics
alternative
mechanisms
proposed.
Nutritional
therapy
vagus
nerve
stimulation
translational
bridges
clinical
treatment
diverse
disorders.
Cell Metabolism,
Год журнала:
2017,
Номер
26(5), С. 719 - 737.e6
Опубликована: Сен. 29, 2017
Elevated
reactive
oxygen
species
(ROS)
induce
the
formation
of
lipids
in
neurons
that
are
transferred
to
glia,
where
they
form
lipid
droplets
(LDs).
We
show
glial
and
neuronal
monocarboxylate
transporters
(MCTs),
fatty
acid
transport
proteins
(FATPs),
apolipoproteins
critical
for
LD
formation.
MCTs
enable
glia
secrete
absorb
lactate,
which
is
converted
pyruvate
acetyl-CoA
neurons.
Lactate
metabolites
provide
a
substrate
synthesis
acids,
processed
by
FATP
apolipoproteins.
In
presence
high
ROS,
inhibiting
lactate
transfer
or
lowering
apolipoprotein
levels
decreases
accumulation
flies
primary
mouse
glial-neuronal
cultures.
human
APOE
can
substitute
fly
APOE4,
an
Alzheimer's
disease
susceptibility
allele,
impaired
promotes
neurodegeneration,
providing
insights
into
mechanisms.
