Biochemical Journal,
Год журнала:
2017,
Номер
474(8), С. 1417 - 1438
Опубликована: Апрель 7, 2017
Approximately
70
human
RNA-binding
proteins
(RBPs)
contain
a
prion-like
domain
(PrLD).
PrLDs
are
low-complexity
domains
that
possess
similar
amino
acid
composition
to
prion
in
yeast,
which
enable
several
proteins,
including
Sup35
and
Rnq1,
form
infectious
conformers,
termed
prions.
In
humans,
contribute
RBP
function
RBPs
undergo
liquid–liquid
phase
transitions
underlie
the
biogenesis
of
various
membraneless
organelles.
However,
this
activity
appears
render
prone
misfolding
aggregation
connected
neurodegenerative
disease.
Indeed,
numerous
with
PrLDs,
TDP-43
(transactivation
response
element
DNA-binding
protein
43),
FUS
(fused
sarcoma),
TAF15
(TATA-binding
protein-associated
factor
15),
EWSR1
(Ewing
sarcoma
breakpoint
region
1),
heterogeneous
nuclear
ribonucleoproteins
A1
A2
(hnRNPA1
hnRNPA2),
have
now
been
via
pathology
genetics
etiology
diseases,
amyotrophic
lateral
sclerosis,
frontotemporal
dementia,
multisystem
proteinopathy.
Here,
we
review
physiological
pathological
roles
most
prominent
PrLDs.
We
also
highlight
potential
disaggregases,
Hsp104,
as
therapeutic
strategy
combat
aberrant
likely
underpin
neurodegeneration.
Journal of Neuroscience,
Год журнала:
2014,
Номер
34(36), С. 11929 - 11947
Опубликована: Сен. 3, 2014
The
major
cell
classes
of
the
brain
differ
in
their
developmental
processes,
metabolism,
signaling,
and
function.
To
better
understand
functions
interactions
types
that
comprise
these
classes,
we
acutely
purified
representative
populations
neurons,
astrocytes,
oligodendrocyte
precursor
cells,
newly
formed
oligodendrocytes,
myelinating
microglia,
endothelial
pericytes
from
mouse
cerebral
cortex.
We
generated
a
transcriptome
database
for
eight
by
RNA
sequencing
used
sensitive
algorithm
to
detect
alternative
splicing
events
each
type.
Bioinformatic
analyses
identified
thousands
new
type-enriched
genes
isoforms
will
provide
novel
markers
identification,
tools
genetic
manipulation,
insights
into
biology
brain.
For
example,
our
data
clues
as
how
neurons
astrocytes
ability
dynamically
regulate
glycolytic
flux
lactate
generation
attributable
unique
PKM2
,
gene
encoding
enzyme
pyruvate
kinase.
This
dataset
powerful
resource
understanding
development
function
ensure
widespread
distribution
datasets,
have
created
user-friendly
website
(
http://web.stanford.edu/group/barres_lab/brain_rnaseq.html
)
provides
platform
analyzing
comparing
transciption
profiles
various
Cell,
Год журнала:
2023,
Номер
186(4), С. 693 - 714
Опубликована: Фев. 1, 2023
Summary
Decades
of
research
have
identified
genetic
factors
and
biochemical
pathways
involved
in
neurodegenerative
diseases
(NDDs).
We
present
evidence
for
the
following
eight
hallmarks
NDD:
pathological
protein
aggregation,
synaptic
neuronal
network
dysfunction,
aberrant
proteostasis,
cytoskeletal
abnormalities,
altered
energy
homeostasis,
DNA
RNA
defects,
inflammation,
cell
death.
describe
hallmarks,
their
biomarkers,
interactions
as
a
framework
to
study
NDDs
using
holistic
approach.
The
can
serve
basis
defining
pathogenic
mechanisms,
categorizing
different
based
on
primary
stratifying
patients
within
specific
NDD,
designing
multi-targeted,
personalized
therapies
effectively
halt
NDDs.
Frontiers in Molecular Neuroscience,
Год журнала:
2019,
Номер
12
Опубликована: Фев. 14, 2019
TAR
DNA
binding
protein
43
(TDP-43)
is
a
versatile
RNA/DNA
involved
in
RNA-related
metabolism.
Hyper-phosphorylated
and
ubiquitinated
TDP-43
deposits
as
inclusion
bodies
the
brain
spinal
cord
of
patients
with
motor
neuron
diseases:
amyotrophic
lateral
sclerosis
(ALS)
frontotemporal
lobar
degeneration
(FTLD).
While
majority
ALS
cases
(90-95%)
are
sporadic
(sALS),
among
familial
5-10%
involve
inheritance
mutations
TARDBP
gene
remaining
due
to
other
genes
such
as:
C9ORF72,
SOD1,
FUS,
NEK1
etc.
Strikingly
however,
(up
97%)
also
contain
deposited
neuronal
inclusions,
which
suggests
its
pivotal
role
pathology.
Thus,
unravelling
molecular
mechanisms
pathology,
seems
central
therapeutics,
hence,
we
comprehensively
review
current
understanding
TDP-43's
pathology
ALS.
We
discuss
roles
mutations,
cytoplasmic
mis-localization
aberrant
post-translational
modifications
Also,
evaluate
amyloid-like
vitro
aggregation,
physiological
versus
pathological
oligomerization
vivo,
liquid-liquid
phase
separation
(LLPS),
potential
prion-like
propagation
propensity
inclusions.
Finally,
describe
various
evolving
TDP-43-induced
toxicity
impairment
endocytosis
mitotoxicity
emerging
strategies
towards
disaggregation
therapeutics.
