Frontiers in Aging Neuroscience,
Journal Year:
2019,
Volume and Issue:
11
Published: Nov. 20, 2019
Neurons
are
highly
specialized
postmitotic
cells
that
inherently
dependent
on
mitochondria
owing
to
their
high
bioenergetic
demand.
Mitochondrial
dysfunction
is
therefore
associated
with
various
age-related
neurodegenerative
disorders
such
as
Alzheimer's
disease
(AD),
wherein
accumulation
of
damaged
and
dysfunctional
has
been
reported
early
symptoms
further
contributing
progression.
In
AD,
impairment
mitochondrial
function
causes
deficiency,
intracellular
calcium
imbalance
oxidative
stress
thereby
aggravating
the
effect
Aβ
tau
pathologies,
leading
synaptic
dysfunction,
cognitive
memory
loss.
Although
there
reports
suggesting
intricate
parallelism
between
AD
pathologies
A
aggregation
hyperphosphorylated
accumulation,
factors
drive
pathogenesis
either
unclear.
addition,
emerging
evidence
suggests
quality
control
(QC)
mechanisms
mitophagy
impaired
in
AD.
As
an
important
QC
mechanism,
plays
a
critical
role
maintaining
neuronal
health
function.
Studies
show
different
proteins
involved
mitophagy,
dynamics
biogenesis
affected
The
compromised
may
also
be
attributed
autophagosome-lysosome
fusion
defects
lysosomal
acidification.
Therapeutic
interventions
aiming
restore
functions
can
used
strategy
for
ameliorating
pathogenesis.
Recent
implicates
microglial
activation
via
induction
reducing
amyloid
plaque
load.
This
review
summarizes
current
developments
field
Molecular Neurodegeneration,
Journal Year:
2020,
Volume and Issue:
15(1)
Published: July 16, 2020
Abstract
Alzheimer’s
disease
(AD)
is
the
most
common
neurodegenerative
disorder
seen
in
age-dependent
dementia.
There
currently
no
effective
treatment
for
AD,
which
may
be
attributed
part
to
lack
of
a
clear
underlying
mechanism.
Studies
within
last
few
decades
provide
growing
evidence
central
role
amyloid
β
(Aβ)
and
tau,
as
well
glial
contributions
various
molecular
cellular
pathways
AD
pathogenesis.
Herein,
we
review
recent
progress
with
respect
Aβ-
tau-associated
mechanisms,
discuss
dysfunction
emphasis
on
neuronal
receptors
that
mediate
Aβ-induced
toxicity.
We
also
other
critical
factors
affect
pathogenesis,
including
genetics,
aging,
variables
related
environment,
lifestyle
habits,
describe
potential
apolipoprotein
E
(APOE),
viral
bacterial
infection,
sleep,
microbiota.
Although
have
gained
much
towards
understanding
aspects
this
devastating
disorder,
greater
commitment
research
mechanism,
diagnostics
will
needed
future
research.
Signal Transduction and Targeted Therapy,
Journal Year:
2020,
Volume and Issue:
5(1)
Published: Oct. 7, 2020
Abstract
Nicotinamide
adenine
dinucleotide
(NAD
+
)
and
its
metabolites
function
as
critical
regulators
to
maintain
physiologic
processes,
enabling
the
plastic
cells
adapt
environmental
changes
including
nutrient
perturbation,
genotoxic
factors,
circadian
disorder,
infection,
inflammation
xenobiotics.
These
effects
are
mainly
achieved
by
driving
effect
of
NAD
on
metabolic
pathways
enzyme
cofactors
transferring
hydrogen
in
oxidation-reduction
reactions.
Besides,
multiple
-dependent
enzymes
involved
physiology
either
post-synthesis
chemical
modification
DNA,
RNA
proteins,
or
releasing
second
messenger
cyclic
ADP-ribose
(cADPR)
NAADP
.
Prolonged
disequilibrium
metabolism
disturbs
physiological
functions,
resulting
diseases
diseases,
cancer,
aging
neurodegeneration
disorder.
In
this
review,
we
summarize
recent
advances
our
understanding
molecular
mechanisms
-regulated
responses
stresses,
contribution
deficiency
various
via
manipulating
cellular
communication
networks
potential
new
avenues
for
therapeutic
intervention.
British Journal of Pharmacology,
Journal Year:
2019,
Volume and Issue:
176(18), P. 3489 - 3507
Published: Jan. 24, 2019
Dysfunction
of
cell
bioenergetics
is
a
common
feature
neurodegenerative
diseases,
the
most
which
Alzheimer's
disease
(AD).
Disrupted
energy
utilization
implicates
mitochondria
at
its
nexus.
This
review
summarizes
some
evidence
that
points
to
faulty
mitochondrial
function
in
AD
and
highlights
past
current
therapeutic
development
efforts.
Classical
neuropathological
hallmarks
(β-amyloid
τ)
sporadic
risk
genes
(APOE)
may
trigger
disturbance,
yet
dysfunction
incite
pathology.
Preclinical
clinical
efforts
have
overwhelmingly
centred
on
amyloid
pathway,
but
trials
reveal
clear-cut
benefits.
therapies
aimed
are
few
concentrate
reversing
oxidative
stress
death
pathways.
Novel
research
boosting
bioenergetic
offer
an
alternative
treatment
strategy.
Enhancing
preclinical
models
yield
widespread
favourable
effects
could
benefit
persons
with
AD.
LINKED
ARTICLES:
article
part
themed
section
Therapeutics
for
Dementia
Disease:
New
Directions
Precision
Medicine.
To
view
other
articles
this
visit
http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc.