Molecules,
Год журнала:
2022,
Номер
27(23), С. 8448 - 8448
Опубликована: Дек. 2, 2022
Neurodegenerative
diseases
constitute
a
broad
range
of
central
nervous
system
disorders,
characterized
by
neuronal
degeneration.
Alzheimer’s
disease,
Parkinson’s
amyolotrophic
lateral
sclerosis
(ALS),
and
progressive
forms
multiple
(MS)
are
some
the
most
frequent
neurodegenerative
diseases.
Despite
their
diversity,
these
share
common
pathophysiological
mechanisms:
abnormal
aggregation
disease-related
misfolded
proteins,
autophagosome–lysosome
pathway
dysregulation,
impaired
ubiquitin–proteasome
system,
oxidative
damage,
mitochondrial
dysfunction
excessive
neuroinflammation.
There
is
still
no
effective
drug
that
could
halt
progression
diseases,
current
treatments
mainly
symptomatic.
In
this
regard,
development
novel
multi-target
pharmaceutical
approaches
presents
an
attractive
therapeutic
strategy.
Ibudilast,
anti-inflammatory
firstly
developed
as
asthma
treatment,
cyclic
nucleotide
phosphodiesterases
(PDEs)
inhibitor,
which
acts
increasing
amount
adenosine
monophosphate
(cAMP)
guanosine
(cGMP),
while
downregulating
pro-inflammatory
factors,
such
tumor
necrosis
factor-α
(TNF-α),
macrophage
migration
inhibitory
factor
(MIF)
Toll-like
receptor
4
(TLR-4).
The
preclinical
evidence
shows
ibudilast
may
act
neuroprotectively
in
suppressing
neuroinflammation,
inhibiting
apoptosis,
regulating
function
affecting
pathways,
well
attenuating
stress.
clinical
trials
ALS
MS
also
show
promising
results.
Herein,
we
aim
to
provide
update
on
emerging
potential
discuss
challenges
suggest
future
directions.
Ageing Research Reviews,
Год журнала:
2024,
Номер
99, С. 102357 - 102357
Опубликована: Июнь 1, 2024
Neurodegenerative
disorders
(NDs)
are
expected
to
pose
a
significant
challenge
for
both
medicine
and
public
health
in
the
upcoming
years
due
global
demographic
changes.
NDs
mainly
represented
by
degeneration/loss
of
neurons,
which
is
primarily
accountable
severe
mental
illness.
This
neuronal
degeneration
leads
many
neuropsychiatric
problems
permanent
disability
an
individual.
Moreover,
tight
junction
brain,
blood-brain
barrier
(BBB)has
protective
feature,
functioning
as
biological
that
can
prevent
medicines,
toxins,
foreign
substances
from
entering
brain.
However,
delivering
any
medicinal
agent
brain
(i.e.,
Multiple
sclerosis,
Alzheimer's,
Parkinson's,
etc.)
enormously
challenging.
There
approved
therapies
address
NDs,
but
most
them
only
help
treat
associated
manifestations.
The
available
have
failed
control
progression
certain
factors,
i.e.,
BBB
drug-associated
undesirable
effects.
extremely
complex
pathology,
with
pathogenic
mechanisms
involved
initiation
progression;
thereby,
limited
survival
rate
has
been
observed
ND
patients.
Hence,
understanding
exact
mechanism
behind
crucial
developing
alternative
approaches
improving
patients'
rates.
Thus,
present
review
sheds
light
on
different
cellular
novel
therapeutic
their
clinical
relevance,
will
assist
researchers
alternate
strategies
limitations
conventional
therapies.
current
work
offers
scope
into
near
future
improve
approach
NDs.
Molecular Neurodegeneration,
Год журнала:
2024,
Номер
19(1)
Опубликована: Янв. 25, 2024
Abstract
The
extracellular
matrix
is
a
richly
bioactive
composition
of
substrates
that
provides
biophysical
stability,
facilitates
intercellular
signaling,
and
both
reflects
governs
the
physiological
status
local
microenvironment.
in
central
nervous
system
(CNS)
far
from
simply
an
inert
scaffold
for
mechanical
support,
instead
conducting
active
role
homeostasis
providing
broad
capacity
adaptation
remodeling
response
to
stress
otherwise
would
challenge
equilibrium
between
neuronal,
glial,
vascular
elements.
A
major
constituent
collagen,
whose
characteristic
triple
helical
structure
renders
biochemical
stability
enable
bidirectional
crosstalk
resident
cells.
Multiple
members
collagen
superfamily
are
critical
neuronal
maturation
circuit
formation,
axon
guidance,
synaptogenesis
brain.
In
mature
tissue,
interacts
with
other
fibrous
proteins
glycoproteins
sustain
three-dimensional
medium
through
which
complex
networks
cells
can
communicate.
While
scaffolding,
CNS
also
highly
dynamic,
multiple
binding
sites
partnering
proteins,
cell-surface
receptors,
ligands.
These
interactions
emerging
as
mediators
disease
injury,
particularly
regarding
changes
stiffness,
astrocyte
recruitment
reactivity,
pro-inflammatory
signaling
microenvironments.
Changes
and/or
deposition
impact
cellular
tissue
biomechanics
brain,
turn
alter
responses
including
antigenicity,
angiogenesis,
gliosis,
immune-related
factors,
each
involving
contribute
limited
regeneration
tissue.
Emerging
therapeutics
attempt
rebuild
using
peptide
fragments,
collagen-enriched
scaffolds
mimetics,
hold
great
potential
promote
neural
repair
regeneration.
Recent
evidence
our
group
others
indicates
repairing
protease-degraded
helices
mimetic
peptides
helps
restore
survival
spectrum
degenerative
conditions.
Restoration
likely
involves
bolstering
stiffness
reduce
reactivity
inflammation
well
inhibitory
immune-signaling
Facilitating
rather
than
endogenous
replacement
degraded
by
or
injury
may
represent
next
frontier
developing
therapies
based
on
protection,
repair,
neurons
system.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(4), С. 1991 - 1991
Опубликована: Фев. 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.
Biomolecules,
Год журнала:
2022,
Номер
12(11), С. 1676 - 1676
Опубликована: Ноя. 11, 2022
Damage
or
loss
of
brain
cells
and
impaired
neurochemistry,
neurogenesis,
synaptic
nonsynaptic
plasticity
the
lead
to
dementia
in
neurodegenerative
diseases,
such
as
Alzheimer's
disease
(AD).
Injury
synapses
neurons
accumulation
extracellular
amyloid
plaques
intracellular
neurofibrillary
tangles
are
considered
main
morphological
neuropathological
features
AD.
Age,
genetic
epigenetic
factors,
environmental
stressors,
lifestyle
contribute
risk
AD
onset
progression.
These
factors
associated
with
structural
functional
changes
brain,
leading
cognitive
decline.
Biomarkers
reflect
cause
specific
function,
especially
pathways
neurotransmission,
neuroinflammation,
bioenergetics,
apoptosis,
oxidative
nitrosative
stress.
Even
initial
stages,
is
Aβ
neurotoxicity,
mitochondrial
dysfunction,
tau
neurotoxicity.
The
integrative
amyloid-tau-mitochondrial
hypothesis
assumes
that
primary
neurotoxicity
oligomers
oligomers,
their
mutual
synergy.
For
development
new
efficient
drugs,
targeting
elimination
potentiation
effects,
unwanted
protein
interactions
biomarkers
(mainly
dysfunction)
early
stage
seems
promising.
Microorganisms,
Год журнала:
2023,
Номер
11(7), С. 1832 - 1832
Опубликована: Июль 18, 2023
Pathogens
that
play
a
role
in
the
development
and
progression
of
periodontitis
have
gained
significant
attention
due
to
their
implications
onset
various
systemic
diseases.
Periodontitis
is
characterized
as
an
inflammatory
disease
gingival
tissue
mainly
caused
by
bacterial
pathogens.
Among
them,
Porphyromonas
gingivalis,
Treponema
denticola,
Fusobacterium
nucleatum,
Aggregatibacter
actinomycetemcomitans,
Tannerella
forsythia
are
regarded
main
periodontal
These
pathogens
elicit
release
cytokines,
which
combination
with
virulence
factors
induce
chronic
inflammation
subsequently
impact
neural
function
while
also
altering
permeability
blood–brain
barrier.
The
primary
objective
this
review
summarize
existing
information
regarding
pathogens,
factors,
potential
association
neuroinflammation
neurodegenerative
We
systematically
reviewed
longitudinal
studies
investigated
between
disorders.
Out
24
examined,
20
showed
some
degree
positive
correlation
disorders,
focusing
on
cognitive
demonstrating
most
robust
effects.
Therefore,
might
represent
exciting
new
approach
develop
novel
preventive
treatments
for
