Endocrine Reviews,
Год журнала:
2015,
Номер
36(3), С. 305 - 342
Опубликована: Май 7, 2015
Traumatic
brain
injury
(TBI)
is
a
growing
public
health
problem
worldwide
and
leading
cause
of
death
disability.
The
causes
TBI
include
motor
vehicle
accidents,
which
are
the
most
common
cause,
falls,
acts
violence,
sports-related
head
traumas,
war
accidents
including
blast-related
injuries.
Recently,
pituitary
dysfunction
has
also
been
described
in
boxers
kickboxers.
Neuroendocrine
due
to
was
for
first
time
1918.
Only
case
reports
small
series
were
reported
until
2000,
but
since
then
function
victims
investigated
more
detail.
frequency
hypopituitarism
after
varies
widely
among
different
studies
(15–50%
patients
with
studies).
estimates
persistent
decrease
12%
if
repeated
testing
applied.
GH
hormone
lost
TBI,
followed
by
ACTH,
gonadotropins
(FSH
LH),
TSH.
underlying
mechanisms
responsible
not
entirely
clear;
however,
recent
have
shown
that
genetic
predisposition
autoimmunity
may
role.
Hypopituitarism
negative
impact
on
pace
or
degree
functional
recovery
cognition.
What
clear
whether
treatment
beneficial
effect
specific
function.
In
this
review,
current
data
related
anterior
adult
updated,
guidelines
diagnosis,
follow-up
strategies,
therapeutic
approaches
reported.
The
transition
between
soluble
intrinsically
disordered
tau
protein
and
aggregated
in
neurofibrillary
tangles
Alzheimer's
disease
is
unknown.
Here,
we
propose
that
species
can
undergo
liquid-liquid
phase
separation
(LLPS)
under
cellular
conditions
phase-separated
droplets
serve
as
an
intermediate
toward
aggregate
formation.
We
demonstrate
phosphorylated
or
mutant
aggregation
prone
recombinant
undergoes
LLPS,
does
high
molecular
weight
phospho-tau
isolated
from
human
Alzheimer
brain.
Droplet-like
also
be
observed
neurons
other
cells.
found
become
gel-like
minutes,
over
days
start
to
spontaneously
form
thioflavin-S-positive
aggregates
are
competent
of
seeding
aggregation.
Since
analogous
LLPS
observations
have
been
made
for
FUS,
hnRNPA1,
TDP43,
which
the
context
amyotrophic
lateral
sclerosis,
suggest
represents
a
biophysical
process
with
role
multiple
different
neurodegenerative
diseases.
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.
JAMA Neurology,
Год журнала:
2015,
Номер
72(3), С. 355 - 355
Опубликована: Янв. 19, 2015
Importance
Traumatic
brain
injury
(TBI)
is
a
significant
public
health
concern
that
affects
individuals
in
all
demographics.
With
increasing
interest
the
medical
and
communities,
understanding
inflammatory
mechanisms
drive
pathologic
consequent
cognitive
outcomes
can
inform
future
research
clinical
decisions
for
patients
with
TBI.
Objectives
To
review
known
TBI
to
highlight
trials
neuroprotective
therapeutic
manipulations
of
Evidence
Review
We
searched
articles
PubMed
published
between
1960
August
1,
2014,
using
following
keywords:traumatic
injury,
sterile
inflammation,
astrocytes,
microglia,
monocytes,
macrophages,
neutrophils,
T
cells,
reactive
oxygen
species,
alarmins,
danger-associated
molecular
patterns,
purinergic
receptors,
neuroprotection,andclinical
trials.Previous
or
studies
involved
manipulation
discussed
were
considered
inclusion.
The
final
list
selected
was
assembled
based
on
novelty
direct
relevance
primary
focus
this
review.
Findings
diverse
group
injuries
induced
by
secondary
give
rise
cell
death,
neurologic
dysfunction
Pathogenesis
driven
complex,
interacting
include
ion
channel
gap
junction
signaling,
receptor
excitotoxic
neurotransmitter
perturbations
calcium
homeostasis,
damage-associated
pattern
molecules,
among
others.
Central
nervous
system
resident
peripherally
derived
cells
respond
provide
neuroprotection
participate
maladaptive
reactions.
exact
contribution
lesion
dictated
their
anatomical
positioning
as
well
local
cues
which
they
are
exposed.
Conclusions
Relevance
development
those
promote
repair
exceedingly
complex
often
superimposed.
Because
pathogenic
diversify
over
time
even
differ
type,
it
important
therapeutics
be
developed
administered
these
variables
mind.
Due
its
complexity,
has
proven
particularly
challenging
treat;
however,
number
promising
approaches
now
under
pre-clinical
development,
recent
have
yielded
few
successes.
Given
worldwide
impact
human
population,
imperative
remains
active
area
we
continue
develop
improve
outcome
afflicted
patients.
Neurology,
Год журнала:
2013,
Номер
81(13), С. 1122 - 1129
Опубликована: Авг. 22, 2013
The
goal
of
this
study
was
to
examine
the
clinical
presentation
chronic
traumatic
encephalopathy
(CTE)
in
neuropathologically
confirmed
cases.Thirty-six
adult
male
subjects
were
selected
from
all
cases
CTE
at
Boston
University
Center
for
Study
Traumatic
Encephalopathy
brain
bank.
Subjects
athletes,
had
no
comorbid
neurodegenerative
or
motor
neuron
disease,
and
next-of-kin
informants
provide
retrospective
reports
subjects'
histories
presentations.
These
interviews
conducted
blind
neuropathologic
findings.A
triad
cognitive,
behavioral,
mood
impairments
common
overall,
with
cognitive
deficits
reported
almost
subjects.
Three
asymptomatic
time
death.
Consistent
earlier
case
boxers,
2
relatively
distinct
presentations
emerged,
one
group
whose
initial
features
developed
a
younger
age
involved
behavioral
and/or
disturbance
(n
=
22),
another
an
older
impairment
11).This
suggests
there
are
major
CTE,
behavior/mood
variant
other
variant.
PLoS ONE,
Год журнала:
2013,
Номер
8(9), С. e75091 - e75091
Опубликована: Сен. 20, 2013
ObjectiveNeuronal
damage
is
the
morphological
substrate
of
persisting
neurological
disability.
Neurofilaments
(Nf)
are
cytoskeletal
proteins
neurons
and
their
release
into
cerebrospinal
fluid
has
shown
encouraging
results
as
a
biomarker
for
neurodegeneration.
This
study
aimed
to
validate
quantification
Nf
light
chain
(NfL)
in
blood
samples,
biofluid
source
easily
accessible
longitudinal
studies.
MethodsWe
developed
applied
highly
sensitive
electrochemiluminescence
(ECL)
based
immunoassay
NfL
CSF.
ResultsPatients
with
Alzheimer’s
disease
(AD)
(30.8
pg/ml,
n=20),
Guillain-Barré-syndrome
(GBS)
(79.4
n=19)
or
amyotrophic
lateral
sclerosis
(ALS)
(95.4
n=46)
had
higher
serum
values
than
control
group
patients
without
evidence
structural
CNS
(control
patients,
CP)
(4.4
n=68,
p<0.0001
each
comparison,
p=0.002
AD
patients)
healthy
controls
(HC)
(3.3
n=67,
p<0.0001).
Similar
differences
were
seen
corresponding
CSF
samples.
levels
correlated
(r=0.48,
p=0.033),
GBS
(r=0.79,
p<0.0001)
ALS
(r=0.70,
p<0.0001),
but
not
CP
(r=0.11,
p=0.3739).
The
sensitivity
specificity
separating
from
was
91.3%
91.0%.
ConclusionsWe
validated
novel
ECL
sandwich
protein
(NfLUmea47:3);
more
20-fold
controls.
Our
data
supports
further
studies
neurodegenerative
diseases
potential
on-going
progression,
surrogate
quantify
effects
neuroprotective
drugs
clinical
trials.
