Cell Reports Medicine,
Journal Year:
2021,
Volume and Issue:
2(4), P. 100238 - 100238
Published: April 1, 2021
Improved
stem
cell-derived
pancreatic
islet
(SC-islet)
differentiation
protocols
robustly
generate
insulin-secreting
β
cells
from
patient
induced
pluripotent
(iPSCs).
These
advances
are
enabling
in
vitro
disease
modeling
studies
and
the
development
of
an
autologous
diabetes
cell
replacement
therapy.
SC-islet
technology
elucidates
key
features
human
pancreas
progression
through
generation
progenitors,
endocrine
derived
diabetic
nondiabetic
iPSCs.
Combining
with
gene
editing
next-generation
sequencing
reveals
impact
diabetes-causing
mutations
phenotypes
on
multiple
types.
In
addition,
supply
SC-islets,
containing
other
types,
is
unlimited,
presenting
opportunity
for
personalized
medicine
overcoming
several
disadvantages
posed
by
donor
islets.
This
review
highlights
relevant
involving
iPSC-β
encompassing
new
conclusions
patients
therapeutic
potential
cells.
Frontiers in Immunology,
Journal Year:
2020,
Volume and Issue:
11
Published: April 23, 2020
Amyloid
plaques,
mainly
composed
of
abnormally
aggregated
amyloid
β-protein
(Aβ)
in
the
brain
parenchyma,
and
neurofibrillary
tangles
(NFTs),
abnormal
aggregates
hyperphosphorylated
tau
protein
neurons,
are
two
pathological
hallmarks
Alzheimer’s
disease
(AD).
Fibrillar
Aβ
deposits
accompanied
with
neuroinflammation
synapse
loss,
characterized
by
activated
microglia
dystrophic
neurites.
Genome-wide
association
studies
on
patients
late-onset
AD
have
identified
a
dozen
genetic
risk
variants
that
involved
innate
immune
responses,
highlighting
importance
cells
pathogenesis
AD.
Additional
lines
evidence
support
notion
microglia,
central
nervous
system
(CNS),
play
pivotal,
dual
roles
progression:
either
clearing
phagocytosis
promoting
neuron
survival
plasticity
or
releasing
cytotoxic
chemicals,
inflammatory
cytokines,
exacerbating
load
synaptotoxicity.
Aggregated
binds
to
toll-like
receptor
4
(TLR4)
activates
resulting
increased
cytokine
production.
Complement
components
associated
plaques
NFTs.
can
activate
complement,
leading
pruning
loss
microglial
phagocytosis.
Systemic
inflammation
TLR4,
NLRP3
inflammasome,
complement
brain,
neuroinflammation,
accumulation,
neurodegeneration.
The
host
response
has
been
shown
function
through
complex
crosstalk
between
TLR,
inflammasome
signaling
pathways.
Accordingly,
targeting
molecular
mechanisms
underlying
TLR-complement-NLRP3
pathways
be
preventive
therapeutic
approach
for
Physiological Reviews,
Journal Year:
2021,
Volume and Issue:
101(3), P. 1047 - 1081
Published: Jan. 21, 2021
The
history
of
Alzheimer's
disease
(AD)
started
in
1907,
but
we
needed
to
wait
until
the
end
century
identify
components
pathological
hallmarks
and
genetic
subtypes
formulate
first
pathogenic
hypothesis.
Thanks
biomarkers
new
technologies,
concept
AD
then
rapidly
changed
from
a
static
view
an
amnestic
dementia
presenium
biological
entity
that
could
be
clinically
manifested
as
normal
cognition
or
different
types.
What
is
clearly
emerging
studies
heterogeneous
each
aspect,
such
amyloid
composition,
tau
distribution,
relation
between
tau,
clinical
symptoms,
background,
thus
it
probably
impossible
explain
with
single
process.
scientific
approach
suffers
chronological
mismatches
clinical,
pathological,
technological
data,
causing
difficulty
conceiving
diagnostic
gold
standards
creating
models
for
drug
discovery
screening.
A
recent
mathematical
computer-based
offers
opportunity
study
real
life
provide
point
final
missing
pieces
puzzle.
The Journal of Cell Biology,
Journal Year:
2020,
Volume and Issue:
219(11)
Published: Aug. 14, 2020
Mitophagy
is
an
evolutionarily
conserved
process
involving
the
autophagic
targeting
and
clearance
of
mitochondria
destined
for
removal.
Recent
insights
into
complex
nature
overlapping
pathways
regulating
mitophagy
illustrate
mitophagy's
essential
role
in
maintaining
health
mitochondrial
network.
In
this
review,
we
highlight
recent
studies
that
have
changed
way
understood,
from
initiation
through
lysosomal
degradation.
We
outline
numerous
mitophagic
receptors
triggers,
with
a
focus
on
basal
physiologically
relevant
cues,
offering
insight
why
they
lead
to
also
explore
how
maintains
homeostasis
at
organ
system
levels
loss
may
play
diverse
group
diseases,
including
cardiovascular,
metabolic,
neurodegenerative
diseases.
With
disrupted
affecting
such
wide
array
physiological
processes,
deeper
understanding
modulate
could
provide
avenues
therapies.
Human
Alzheimer’s
disease
(AD)
brains
and
transgenic
AD
mouse
models
manifest
hyperexcitability.
This
aberrant
electrical
activity
is
caused
by
synaptic
dysfunction
that
represents
the
major
pathophysiological
correlate
of
cognitive
decline.
However,
underlying
mechanism
for
this
excessive
excitability
remains
incompletely
understood.
To
investigate
basis
hyperactivity,
we
performed
electrophysiological
immunofluorescence
studies
on
hiPSC-derived
cerebrocortical
neuronal
cultures
cerebral
organoids
bearing
AD-related
mutations
in
presenilin-1
or
amyloid
precursor
protein
vs.
isogenic
gene
corrected
controls.
In
neurons/organoids,
found
increased
excitatory
bursting
activity,
which
could
be
explained
part
a
decrease
neurite
length.
neurons
also
displayed
sodium
current
density
decreased
inhibitory
activity.
Our
findings
establish
as
relevant
model
early
pathophysiology
provide
mechanistic
insight
into
observed
Molecular Neurodegeneration,
Journal Year:
2021,
Volume and Issue:
16(1)
Published: Aug. 12, 2021
Mass
spectrometry-based
proteomics
empowers
deep
profiling
of
proteome
and
protein
posttranslational
modifications
(PTMs)
in
Alzheimer's
disease
(AD).
Here
we
review
the
advances
limitations
historic
recent
AD
proteomic
research.
Complementary
to
genetic
mapping,
studies
not
only
validate
canonical
amyloid
tau
pathways,
but
also
uncover
novel
components
broad
networks,
such
as
RNA
splicing,
development,
immunity,
membrane
transport,
lipid
metabolism,
synaptic
function,
mitochondrial
activity.
Meta-analysis
seven
datasets
reveals
2,698
differentially
expressed
(DE)
proteins
landscape
brain
(n
=
12,017
proteins/genes),
covering
35
reported
genes
risk
loci.
The
DE
contain
cellular
markers
enriched
neurons,
microglia,
astrocytes,
oligodendrocytes,
epithelial
cells,
supporting
involvement
diverse
cell
types
pathology.
We
discuss
hypothesized
protective
or
detrimental
roles
selected
proteins,
emphasizing
top
"amyloidome"
(all
biomolecules
plaques)
progression.
Comprehensive
PTM
analysis
represents
another
layer
molecular
events
AD.
In
particular,
PTMs
are
correlated
with
stages
indicate
heterogeneity
individual
patients.
Moreover,
unprecedented
coverage
biofluids,
cerebrospinal
fluid
serum,
procures
putative
biomarkers
through
meta-analysis.
Thus,
proteomics-driven
systems
biology
presents
a
new
frontier
link
genotype,
proteotype,
phenotype,
accelerating
development
improved
models
treatment
strategies.
International Journal of Molecular Sciences,
Journal Year:
2021,
Volume and Issue:
22(4), P. 2153 - 2153
Published: Feb. 22, 2021
Neurodegenerative
diseases
resulting
from
the
progressive
loss
of
structure
and/or
function
neurons
contribute
to
different
paralysis
degrees
and
cognition
sensation.
The
lack
successful
curative
therapies
for
neurodegenerative
disorders
leads
a
considerable
burden
on
society
high
economic
impact.
Over
past
20
years,
regenerative
cell
therapy,
also
known
as
stem
has
provided
an
excellent
opportunity
investigate
potentially
powerful
innovative
strategies
treating
diseases.
This
is
due
cells’
capability
repair
injured
neuronal
tissue
by
replacing
damaged
or
lost
cells
with
differentiated
cells,
providing
conducive
environment
that
in
favor
regeneration,
protecting
existing
healthy
glial
further
damage.
Thus,
this
review,
various
types
current
knowledge
stem-cell-based
diseases,
recent
advances
field
are
summarized.
Indeed,
better
understanding
studies
technologies
cause
progress
into
realistic
efficacious
treatments
disorders.
Advanced Science,
Journal Year:
2021,
Volume and Issue:
8(18)
Published: Aug. 2, 2021
Alzheimer's
disease
(AD)
is
a
progressive
neurodegenerative
with
no
cure.
Huge
efforts
have
been
made
to
develop
anti-AD
drugs
in
the
past
decades.
However,
all
drug
development
programs
for
disease-modifying
therapies
failed.
Possible
reasons
high
failure
rate
include
incomplete
understanding
of
complex
pathophysiology
AD,
especially
sporadic
AD
(sAD),
and
species
difference
between
humans
animal
models
used
preclinical
studies.
In
this
study,
sAD
modeled
using
human
induced
pluripotent
stem
cell
(hiPSC)-derived
3D
brain
organoids.
Because
blood-brain
barrier
(BBB)
leakage
well-known
risk
factor
organoids
are
exposed
serum
mimic
exposure
consequence
BBB
breakdown
patient
brains.
The
serum-exposed
able
recapitulate
AD-like
pathologies,
including
increased
amyloid
beta
(Aβ)
aggregates
phosphorylated
microtubule-associated
tau
protein
(p-Tau)
level,
synaptic
loss,
impaired
neural
network.
Serum
increases
Aβ
p-Tau
levels
through
inducing
beta-secretase
1
(BACE)
glycogen
synthase
kinase-3
alpha
/
(GSK3α/β)
levels,
respectively.
addition,
single-cell
transcriptomic
analysis
reveals
that
reduced
function
both
neurons
astrocytes
immune
response
astrocytes.
organoid-based
model
established
study
can
provide
powerful
platform
mechanistic
therapeutic
future.