Journal of Neuroscience,
Journal Year:
2016,
Volume and Issue:
36(4), P. 1071 - 1085
Published: Jan. 27, 2016
In
cultured
vertebrate
neurons,
axons
have
a
uniform
arrangement
of
microtubules
with
plus-ends
distal
to
the
cell
body
(plus-end-out),
whereas
dendrites
contain
mixed
polarity
orientations
both
plus-end-out
and
minus-end-out
oriented
microtubules.
Rather
than
non-uniform
microtubules,
uniparallel
are
signature
in
Drosophila
Caenorhabditis
elegans
neurons.
To
determine
whether
microtubule
organization
is
conserved
feature
dendrites,
we
used
live-cell
imaging
systematically
analyze
plus-end
primary
cultures
rat
hippocampal
cortical
dentate
granule
cells
mouse
organotypic
slices,
layer
2/3
pyramidal
neurons
somatosensory
cortex
living
mice.
vitro
vivo
,
all
had
orientation
axons,
orientations.
When
dendritic
were
severed
by
laser-based
microsurgery,
detected
equal
numbers
plus-
throughout
processes.
generally
more
stable
comparable
axons.
Interestingly,
at
early
stages
neuronal
development
nonpolarized
cells,
newly
formed
neurites
already
contained
opposite
polarity,
suggesting
that
establishment
occurs
during
axon
formation.
We
propose
model
which
selective
formation
critical
process
underlying
polarization.
SIGNIFICANCE
STATEMENT
Live-cell
was
neuron
specific
only
Based
on
these
findings,
authors
Chemical Reviews,
Journal Year:
2018,
Volume and Issue:
119(2), P. 1221 - 1322
Published: Aug. 10, 2018
Neurodegenerative
diseases
pose
a
substantial
socioeconomic
burden
on
society.
Unfortunately,
the
aging
world
population
and
lack
of
effective
cures
foreshadow
negative
outlook.
Although
large
amount
research
has
been
dedicated
to
elucidating
pathologies
neurodegenerative
diseases,
their
principal
causes
remain
elusive.
Metal
ion
dyshomeostasis,
proteopathy,
oxidative
stress,
neurotransmitter
deficiencies
are
pathological
features
shared
across
multiple
disorders.
In
addition,
these
factors
proposed
be
interrelated
upon
disease
progression.
Thus,
development
multifunctional
compounds
capable
simultaneously
interacting
with
several
components
suggested
as
solution
undertake
complex
diseases.
this
review,
we
outline
discuss
possible
therapeutic
targets
in
Alzheimer's
disease,
Parkinson's
amyotrophic
lateral
sclerosis
molecules,
previously
designed
or
discovered
potential
drug
candidates
for
disorders
emphasis
multifunctionality.
underrepresented
areas
discussed
indicate
new
directions.
Molecular Therapy,
Journal Year:
2016,
Volume and Issue:
24(10), P. 1836 - 1847
Published: Aug. 10, 2016
Delivery
represents
a
significant
barrier
to
the
clinical
advancement
of
oligonucleotide
therapeutics
for
treatment
neurological
disorders,
such
as
Huntington's
disease.
Small,
endogenous
vesicles
known
exosomes
have
potential
act
delivery
vehicles,
but
robust
and
scalable
methods
loading
RNA
therapeutic
cargo
into
are
lacking.
Here,
we
show
that
hydrophobically
modified
small
interfering
RNAs
(hsiRNAs)
efficiently
load
upon
co-incubation,
without
altering
vesicle
size
distribution
or
integrity.
Exosomes
loaded
with
hsiRNAs
targeting
Huntingtin
mRNA
were
internalized
by
mouse
primary
cortical
neurons
promoted
dose-dependent
silencing
protein.
Unilateral
infusion
hsiRNA-loaded
exosomes,
not
alone,
striatum
resulted
in
bilateral
statistically
up
35%
mRNA.
The
broad
efficacy
delivered
brain
is
expected
advance
development
therapies
disease
other
neurodegenerative
disorders.
Science,
Journal Year:
2019,
Volume and Issue:
364(6441)
Published: May 16, 2019
Local
translation
in
presynaptic
terminals
Proteins
carry
out
most
of
the
functions
cells,
including
neurons,
which
are
one
morphologically
complex
cell
types
body.
This
poses
challenges
for
how
proteins
can
be
supplied
to
remote
regions
where
connections
(synapses)
made
with
other
neurons.
One
solution
neuron
protein-supply
problem
involves
local
synthesis
from
messenger
RNA
(mRNA)
molecules
located
at
or
near
synapses.
Hafner
et
al.
used
sequencing
methods
and
superresolution
microscopy
show
that
axon
contain
hundreds
mRNA
as
well
machinery
needed
protein
synthesis.
Furthermore,
were
able
use
these
components
make
participate
synaptic
transmission.
Science
,
this
issue
p.
eaau3644
Proceedings of the National Academy of Sciences,
Journal Year:
2015,
Volume and Issue:
112(28)
Published: June 29, 2015
Significance
Amyloid
plaques,
a
key
feature
of
Alzheimer’s
disease
brain
pathology,
comprise
an
extracellular
β-amyloid
core
surrounded
by
tissue
enriched
in
lysosome-like
organelles.
As
foundation
for
understanding
the
mechanisms
that
drive
amyloid
plaque
formation,
we
have
elucidated
cellular
origins
and
molecular
composition
such
The
majority
lysosomes
at
plaques
reside
within
swollen
neuronal
axons.
Interestingly,
these
organelles
contain
low
levels
multiple
luminal
lysosomal
proteases
closely
resemble
lysosome
subpopulation
naturally
occurs
distal
processes.
These
results
suggest
deposits
cause
local
impairment
retrograde
axonal
transport,
leading
to
accumulation
precursors
blockade
their
further
maturation
has
implications
both
production
clearance.
European Journal of Pharmaceutics and Biopharmaceutics,
Journal Year:
2018,
Volume and Issue:
128, P. 337 - 362
Published: May 4, 2018
Central
nervous
system
(CNS)
disorders
(e.g.,
multiple
sclerosis,
Alzheimer's
disease,
etc.)
represent
a
growing
public
health
issue,
primarily
due
to
the
increased
life
expectancy
and
aging
population.
The
treatment
of
such
is
notably
elaborate
requires
delivery
therapeutics
brain
in
appropriate
amounts
elicit
pharmacological
response.
However,
despite
major
advances
both
neuroscience
drug
research,
administration
drugs
CNS
still
remains
elusive.
It
commonly
accepted
that
effectiveness-related
issues
arise
inability
parenterally
administered
macromolecules
cross
Blood-Brain
Barrier
(BBB)
order
access
CNS,
thus
impeding
their
successful
tissues.
As
result,
direct
Nose-to-Brain
has
emerged
as
powerful
strategy
circumvent
BBB
deliver
brain.
present
review
article
attempts
highlight
different
experimental
computational
approaches
pursued
so
far
attain
enhance
therapeutic
agents
shed
some
light
on
underlying
mechanisms
involved
pathogenesis
neurological
disorders.
