动物学研究,
Год журнала:
2024,
Номер
45(2), С. 263 - 274
Опубликована: Янв. 1, 2024
Neurodegenerative
diseases
(NDs)
are
a
group
of
debilitating
neurological
disorders
that
primarily
affect
elderly
populations
and
include
Alzheimer's
disease
(AD),
Parkinson's
(PD),
Huntington's
(HD),
amyotrophic
lateral
sclerosis
(ALS).
Currently,
there
no
therapies
available
can
delay,
stop,
or
reverse
the
pathological
progression
NDs
in
clinical
settings.
As
population
ages,
imposing
huge
burden
on
public
health
systems
affected
families.
Animal
models
important
tools
for
preclinical
investigations
to
understand
pathogenesis
test
potential
treatments.
While
numerous
rodent
have
been
developed
enhance
our
understanding
mechanisms,
limited
success
translating
findings
from
animal
practice
suggests
is
still
need
bridge
this
translation
gap.
Old
World
non-human
primates
(NHPs),
such
as
rhesus,
cynomolgus,
vervet
monkeys,
phylogenetically,
physiologically,
biochemically,
behaviorally
most
relevant
humans.
This
particularly
evident
similarity
structure
function
their
central
nervous
systems,
rendering
species
uniquely
valuable
neuroscience
research.
Recently,
development
several
genetically
modified
NHP
has
successfully
recapitulated
key
pathologies
revealed
novel
mechanisms.
review
focuses
efficacy
NHPs
modeling
insights
gained,
well
challenges
associated
with
generation
complexities
involved
subsequent
analysis.
Journal of Clinical Investigation,
Год журнала:
2022,
Номер
132(10)
Опубликована: Май 15, 2022
Alzheimer's
disease
and
related
dementias
(ADRD)
are
among
the
top
contributors
to
disability
mortality
in
later
life.
As
with
many
chronic
conditions,
aging
is
single
most
influential
factor
development
of
ADRD.
Even
older
adults
who
remain
free
dementia
throughout
their
lives,
cognitive
decline
neurodegenerative
changes
appreciable
advancing
age,
suggesting
shared
pathophysiological
mechanisms.
In
this
Review,
we
provide
an
overview
cognition,
brain
morphology,
neuropathological
protein
accumulation
across
lifespan
humans,
complementary
mechanistic
evidence
from
animal
models.
Next,
highlight
selected
processes
that
differentially
regulated
disease,
including
aberrant
autophagy,
mitochondrial
dysfunction,
cellular
senescence,
epigenetic
changes,
cerebrovascular
inflammation,
lipid
dysregulation.
We
summarize
research
clinical
translational
studies
link
biological
underlying
ADRD
pathogenesis.
Targeting
fundamental
may
represent
a
yet
relatively
unexplored
avenue
attenuate
both
age-related
Collaboration
fields
geroscience
neuroscience,
coupled
new
models
more
closely
align
human
processes,
necessary
advance
novel
therapeutic
discovery
realm.
Abstract
Alzheimer’s
disease
(AD)
is
a
genetically
complex
and
heterogeneous
disorder
with
multifaceted
neuropathological
features,
including
β-amyloid
plaques,
neurofibrillary
tangles,
neuroinflammation.
Over
the
past
decade,
emerging
evidence
has
implicated
both
beneficial
pathological
roles
for
innate
immune
genes
cells,
peripheral
cells
such
as
T
which
can
infiltrate
brain
either
ameliorate
or
exacerbate
AD
neuropathogenesis.
These
findings
support
neuroimmune
axis
of
AD,
in
interplay
adaptive
systems
inside
outside
critically
impacts
etiology
pathogenesis
AD.
In
this
review,
we
discuss
complexities
neuropathology
at
levels
genetics
cellular
physiology,
highlighting
signaling
pathways
associated
risk
interactions
among
brain.
We
emphasize
role
mechanisms
by
monocytes,
influence
neuropathology,
microglial
clearance
amyloid-β
peptide,
key
component
plaque
cores,
pro-inflammatory
cytotoxic
activity
microglia,
astrogliosis,
their
vasculature.
Finally,
review
challenges
outlook
establishing
immune-based
therapies
treating
preventing
Signal Transduction and Targeted Therapy,
Год журнала:
2024,
Номер
9(1)
Опубликована: Янв. 1, 2024
Abstract
Combining
existing
drug
therapy
is
essential
in
developing
new
therapeutic
agents
disease
prevention
and
treatment.
In
preclinical
investigations,
combined
effect
of
certain
known
drugs
has
been
well
established
treating
extensive
human
diseases.
Attributed
to
synergistic
effects
by
targeting
various
pathways
advantages,
such
as
reduced
administration
dose,
decreased
toxicity,
alleviated
resistance,
combinatorial
treatment
now
being
pursued
delivering
combat
major
clinical
illnesses,
cancer,
atherosclerosis,
pulmonary
hypertension,
myocarditis,
rheumatoid
arthritis,
inflammatory
bowel
disease,
metabolic
disorders
neurodegenerative
Combinatorial
involves
combining
or
co-delivering
two
more
for
a
specific
disease.
Nanoparticle
(NP)-mediated
delivery
systems,
i.e.,
liposomal
NPs,
polymeric
NPs
nanocrystals,
are
great
interest
wide
range
due
targeted
delivery,
extended
release,
higher
stability
avoid
rapid
clearance
at
infected
areas.
This
review
summarizes
targets
diseases,
clinically
approved
combinations
the
development
multifunctional
emphasizes
strategies
based
on
severe
Ultimately,
we
discuss
challenging
NP-codelivery
translation
provide
potential
approaches
address
limitations.
offers
comprehensive
overview
recent
cutting-edge
NP-mediated
combination
Nature Communications,
Год журнала:
2021,
Номер
12(1)
Опубликована: Окт. 29, 2021
Abstract
Recent
findings
in
human
samples
and
animal
models
support
the
involvement
of
inflammation
development
Parkinson’s
disease.
Nevertheless,
it
is
currently
unknown
whether
microglial
activation
constitutes
a
primary
event
neurodegeneration.
We
generated
new
mouse
model
by
lentiviral-mediated
selective
α-synuclein
(αSYN)
accumulation
cells.
Surprisingly,
these
mice
developed
progressive
degeneration
dopaminergic
(DA)
neurons
without
endogenous
αSYN
aggregation.
Transcriptomics
functional
assessment
revealed
that
αSYN-accumulating
cells
strong
reactive
state
with
phagocytic
exhaustion
excessive
production
oxidative
proinflammatory
molecules.
This
inflammatory
created
molecular
feed-forward
vicious
cycle
between
microglia
IFNγ-secreting
immune
infiltrating
brain
parenchyma.
Pharmacological
inhibition
nitrosative
molecule
was
sufficient
to
attenuate
These
results
suggest
induces
DA
neuronal
promoting
exhaustion,
an
excessively
toxic
environment
recruitment
peripheral
Disease Models & Mechanisms,
Год журнала:
2021,
Номер
14(6)
Опубликована: Июнь 1, 2021
Mitochondria
are
organelles
with
vital
functions
in
almost
all
eukaryotic
cells.
Often
described
as
the
cellular
'powerhouses'
due
to
their
essential
role
aerobic
oxidative
phosphorylation,
mitochondria
perform
many
other
beyond
energy
production.
As
signaling
organelles,
communicate
nucleus
and
help
maintain
homeostasis,
allow
adaptation
diverse
stresses,
steer
cell
fate
decisions
during
development.
have
taken
center
stage
research
of
normal
pathological
processes,
including
tissue
homeostasis
metabolism,
neurodegeneration,
immunity
infectious
diseases.
The
central
that
assume
within
cells
is
evidenced
by
broad
impact
mitochondrial
diseases,
caused
defects
either
or
nuclear
genes
encoding
for
proteins,
on
different
organ
systems.
In
this
Review,
we
will
provide
reader
a
foundation
'hardware',
mitochondrion
itself,
its
specific
dynamics,
quality
control
mechanisms
cross-organelle
communication,
roles
driver
an
innate
immune
response,
focus
development,
disease
aging.
We
further
discuss
how
DNA
inherited,
mutation
affects
organismal
fitness,
current
therapeutic
approaches
diseases
both
model
organisms
humans.
Frontiers in Aging Neuroscience,
Год журнала:
2023,
Номер
15
Опубликована: Июнь 15, 2023
Alzheimer’s
disease
(AD)
is
a
neurodegenerative
disorder
characterized
by
protein
aggregation
in
the
brain.
Recent
studies
have
revealed
critical
role
of
microglia
AD
pathogenesis.
This
review
provides
comprehensive
summary
current
understanding
microglial
involvement
AD,
focusing
on
genetic
determinants,
phenotypic
state,
phagocytic
capacity,
neuroinflammatory
response,
and
impact
synaptic
plasticity
neuronal
regulation.
Furthermore,
recent
developments
drug
discovery
targeting
are
reviewed,
highlighting
potential
avenues
for
therapeutic
intervention.
emphasizes
essential
insights
into
treatments.
