Brain Sciences,
Journal Year:
2025,
Volume and Issue:
15(3), P. 322 - 322
Published: March 19, 2025
Alzheimer’s
disease
(AD)
represents
a
significant
challenge
among
neurodegenerative
disorders,
as
effective
treatments
and
therapies
remain
largely
undeveloped.
Despite
extensive
research
efforts
employing
various
methodologies
diverse
genetic
models
focused
on
amyloid-β
(Aβ)
pathology,
the
for
therapeutic
strategies
remains
inconclusive.
The
key
pathological
features
of
AD
include
Aβ
senile
plaques,
neurofibrillary
tangles
(NFTs),
activation
neuroinflammatory
pathways.
Presently,
investigations
into
assessing
potential
predominantly
utilize
transgenic
models.
Conversely,
non-transgenic
may
provide
valuable
insights
multifaceted
states
associated
with
AD.
Thus,
these
serve
practical
complementary
tools
evaluating
intervention
strategies,
since
primary
risk
factors
are
most
frequently
modeled.
This
review
aims
to
critically
assess
existing
literature
induced
by
streptozotocin,
scopolamine,
aging,
mechanical
stress,
metals,
dietary
patterns
enhance
their
application
in
research.
Alternatives to Laboratory Animals,
Journal Year:
2023,
Volume and Issue:
51(2), P. 102 - 135
Published: March 1, 2023
The
failure
rate
for
the
translation
of
drugs
from
animal
testing
to
human
treatments
remains
at
over
92%,
where
it
has
been
past
few
decades.
majority
these
failures
are
due
unexpected
toxicity
—
that
is,
safety
issues
revealed
in
trials
were
not
apparent
tests
or
lack
efficacy.
However,
use
more
innovative
tools,
such
as
organs-on-chips,
preclinical
pipeline
drug
testing,
tools
able
predict
events
prior
clinical
and
so
can
be
used
this,
well
efficacy
testing.
Here,
we
review
several
disease
areas,
consider
how
models
failed
offer
effective
new
treatments.
We
also
make
some
suggestions
human-relevant
approach
methodologies
might
applied
address
this.
Journal of Neuroimmunology,
Journal Year:
2024,
Volume and Issue:
390, P. 578342 - 578342
Published: April 5, 2024
Alzheimer's
disease
(AD)
is
a
neurodegenerative
characterized
by
cognitive
decline
that
severely
affects
patients
and
their
families.
Genetic
environmental
risk
factors,
such
as
viral
infections,
synergize
to
accelerate
the
aging-associated
neurodegeneration.
factors
for
late-onset
AD
(LOAD),
which
accounts
most
cases,
are
predominantly
implicated
in
microglial
immune
cell
functions.
As
such,
microglia
play
major
role
amyloid
beta
(Aβ)
plaque
(the
pathological
hallmark
of
AD)
formation.
This
review
aims
provide
an
overview
current
knowledge
regarding
Aβ
formation,
well
impact
on
morphological
functional
diversity
plaques.
Based
this
discussion,
we
seek
identify
challenges
opportunities
field
with
potential
therapeutic
implications.
Annual Review of Immunology,
Journal Year:
2024,
Volume and Issue:
42(1), P. 585 - 613
Published: March 1, 2024
Alzheimer
disease
(AD)
is
the
most
common
neurodegenerative
disease,
and
with
no
efficient
curative
treatment
available,
its
medical,
social,
economic
burdens
are
expected
to
dramatically
increase.
AD
historically
characterized
by
amyloid
β
(Aβ)
plaques
tau
neurofibrillary
tangles,
but
over
last
25
years
chronic
immune
activation
has
been
identified
as
an
important
factor
contributing
pathogenesis.
In
this
article,
we
review
recent
advances
in
our
understanding
of
significance
development
AD.
We
describe
how
brain-resident
macrophages,
microglia,
able
detect
Aβ
species
be
activated,
well
consequences
activated
microglia
discuss
transcriptional
changes
AD,
their
unique
heterogeneity
humans,
emerging
strategies
study
human
microglia.
Finally,
expose,
beyond
role
peripheral
signals
different
cell
types
activation.
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(12), P. 6766 - 6766
Published: June 20, 2024
The
5xFAD
transgenic
mouse
model
widely
used
in
Alzheimer’s
disease
(AD)
research
recapitulates
many
AD-related
phenotypes
with
a
relatively
early
onset
and
aggressive
age-dependent
progression.
Besides
developing
amyloid
peptide
deposits
alongside
neuroinflammation
by
the
age
of
2
months,
as
well
exhibiting
neuronal
decline
4
months
that
intensifies
9
these
mice
manifest
broad
spectrum
behavioural
impairments.
In
this
review,
we
present
extensive
repertoire
dysfunctions
mice,
organised
into
four
categories:
motor
skills,
sensory
function,
learning
memory
abilities,
neuropsychiatric-like
symptoms.
problems,
associated
agility
reflex
movements,
balance
coordination,
skeletal
muscle
typically
arise
time
reach
age.
function
(such
taste,
smell,
hearing,
vision)
starts
to
deteriorate
when
buildups
spread
related
anatomical
structures.
cognitive
functions,
encompassing
such
visual
recognition,
associative,
spatial
working,
reference
learning,
show
signs
from
6
Concerning
symptoms,
comprising
apathy,
anxiety
depression,
willingness
for
exploratory
behaviour,
it
is
believed
motivational
changes
emerge
approximately
Unfortunately,
numerous
studies
different
laboratories
are
often
contradictory
on
conclusions
drawn
identification
age,
making
preclinical
rodent
models
not
easily
translatable
humans.
This
variability
likely
due
range
factors
animals
themselves,
housing
husbandry
conditions,
experimental
settings.
forthcoming
studies,
greater
clarity
details
conducting
testing
could
minimise
inconsistencies
ensure
reliability
reproducibility
results.
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(4), P. 1991 - 1991
Published: Feb. 6, 2024
The
hippocampus
is
a
critical
brain
substrate
for
learning
and
memory;
events
that
harm
the
can
seriously
impair
mental
behavioral
functioning.
Hippocampal
pathophysiologies
have
been
identified
as
potential
causes
effects
of
remarkably
diverse
array
medical
diseases,
psychological
disorders,
environmental
sources
damage.
It
may
be
more
vulnerable
than
other
areas
to
insults
are
related
these
conditions.
One
purpose
this
review
assess
vulnerability
most
prevalent
types
in
multiple
biomedical
domains
(i.e.,
neuroactive
pathogens,
neurotoxins,
neurological
conditions,
trauma,
aging,
neurodegenerative
disease,
acquired
injury,
health
endocrine
developmental
disabilities,
nutrition)
evaluate
whether
affect
first
prominently
compared
loci.
A
second
consider
role
hippocampal
blood–brain
barrier
(BBB)
breakdown
either
causing
or
worsening
harmful
each
insult.
Recent
research
suggests
BBB
fragile
also
prone
disruption
transport
mechanisms
act
maintain
internal
milieu.
Moreover,
compromised
could
factor
common
many
different
insults.
Our
analysis
indicates
parts
brain,
developing
interventions
protect
help
prevent
ameliorate
on
memory
cognition.
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
25(5), P. 2805 - 2805
Published: Feb. 28, 2024
Alzheimer’s
disease
(AD),
the
leading
cause
of
dementia,
presents
a
significant
global
health
challenge
with
no
known
cure
to
date.
Central
our
understanding
AD
pathogenesis
is
β-amyloid
cascade
hypothesis,
which
underlies
drug
research
and
discovery
efforts.
Despite
extensive
studies,
animal
models
have
completely
validated
this
hypothesis.
Effective
are
essential
for
accurately
replicating
key
pathological
features
disease,
notably
formation
plaques
neurofibrillary
tangles.
These
markers
primarily
driven
by
mutations
in
amyloid
precursor
protein
(APP)
presenilin
1
(PS1)
genes
familial
(FAD)
tau
tangle
pathology.
Transgenic
mice
been
instrumental
research,
heavily
relying
on
overexpression
mutated
APP
simulate
conditions.
However,
these
do
not
entirely
replicate
human
condition
AD.
This
review
aims
provide
comprehensive
evaluation
historical
ongoing
efforts
AD,
particularly
through
use
transgenic
models.
It
focused
benefits
gathered
from
toxicity
broader
biological
underpinnings
Additionally,
critically
assesses
application
preclinical
testing
new
therapeutic
interventions,
highlighting
gap
between
clinical
realities.
analysis
underscores
need
refinement
methodologies
bridge
enhance
translational
value
studies.
Glia,
Journal Year:
2025,
Volume and Issue:
73(3), P. 519 - 538
Published: Jan. 6, 2025
Human
genetics
studies
lent
firm
evidence
that
microglia
are
key
to
Alzheimer's
disease
(AD)
pathogenesis
over
a
decade
ago
following
the
identification
of
AD-associated
genes
expressed
in
microglia-specific
manner.
However,
while
alterations
microglial
morphology
and
gene
expression
observed
human
postmortem
brain
tissue,
mechanisms
by
which
drive
contribute
AD
pathology
remain
ill-defined.
Numerous
mouse
models
have
been
developed
facilitate
disambiguation
biological
underlying
AD,
incorporating
amyloidosis,
phosphorylated
tau,
or
both.
Over
time,
use
multiple
technologies
including
bulk
tissue
single
cell
transcriptomics,
epigenomics,
spatial
proteomics,
lipidomics,
metabolomics
shed
light
on
heterogeneity
phenotypes
molecular
patterns
altered
models.
Each
these
'omics
provide
unique
information
insight.
Here,
we
review
literature
approaches
findings
methods
synthesis
knowledge
generated
applying
AD.
International Journal of Molecular Sciences,
Journal Year:
2023,
Volume and Issue:
24(1), P. 823 - 823
Published: Jan. 3, 2023
Modern
pharmacotherapy
of
neurodegenerative
diseases
is
predominantly
symptomatic
and
does
not
allow
vicious
circles
causing
disease
development
to
break.
Protein
misfolding
considered
the
most
important
pathogenetic
factor
diseases.
Physiological
mechanisms
related
function
chaperones,
which
contribute
restoration
native
conformation
functionally
proteins,
evolved
evolutionarily.
These
can
be
promising
for
pharmacological
regulation.
Therefore,
aim
this
review
was
analyze
endoplasmic
reticulum
stress
(ER
stress)
unfolded
protein
response
(UPR)
in
pathogenesis
Data
on
BiP
Sigma1R
chaperones
clinical
experimental
studies
Alzheimer's
disease,
Parkinson's
amyotrophic
lateral
sclerosis,
Huntington's
are
presented.
The
possibility
neuroprotective
effect
dependent
ligand
activation
these
also
demonstrated.
interaction
between
BiP-associated
signaling
neuroprotection
discussed.
performed
analysis
suggests
feasibility
regulation
chaperone
function,
order
achieve
a
effect,
need
further
conjugation
cellular
controlled
by
chaperones.
