Research Square (Research Square),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Oct. 19, 2023
Abstract
Introduction:
Neurodegenerative
disorders,
characterized
by
progressive
neuronal
loss,
remain
a
significant
clinical
challenge
due
to
their
multifactorial
etiology.
While
numerous
enzymes
have
been
implicated
in
pathogenesis,
there
remains
knowledge
gap
regarding
the
precise
biochemical
roles
of
several
novel
enzyme
targets.
Methods:
This
study
encompassed
multi-pronged
approach,
involving
patient-derived
samples
from
Alzheimer's
and
Parkinson's
cases
(n=156),
an
ALS
mouse
model
(n=50),
CRISPR-Cas9
edited
Huntington's
Disease
zebrafish
(n=100).
Enzyme
activity
assays,
localization
microscopy,
interaction
pathway
analyses
were
conducted.
Results:
Elevated
Aminotransferases
was
observed
78%
compared
controls
(p<0.05).
The
revealed
30%
reduction
motor
neuron
counts
tandem
with
altered
(p<0.01).
successfully
displayed
genetic
markers
post-CRISPR
editing,
indicating
95%
editing
efficiency.
Furthermore,
interactions
between
established
neurodegenerative
pathways
identified.
Conclusion:
Mine
findings
highlight
pivotal
role
targets
offering
potential
avenues
for
early
detection
therapeutic
interventions.
intricate
interplay
these
known
disease
underscores
need
integrated
approach
understand
mechanisms
holistically.
MedComm,
Journal Year:
2024,
Volume and Issue:
5(11)
Published: Nov. 1, 2024
Abstract
Identification
of
therapeutic
targets
can
directly
elucidate
the
mechanism
and
effect
drug
therapy,
which
is
a
central
step
in
development.
The
disconnect
between
protein
phenotypes
under
complex
mechanisms
hampers
comprehensive
target
understanding.
Metabolomics,
as
systems
biology
tool
that
captures
phenotypic
changes
induced
by
exogenous
compounds,
has
emerged
valuable
approach
for
identification.
A
overview
was
provided
this
review
to
illustrate
principles
advantages
metabolomics,
delving
into
application
metabolomics
This
outlines
various
metabolomics‐based
methods,
such
dose–response
stable
isotope‐resolved
multiomics,
identify
key
enzymes
metabolic
pathways
affected
substances
through
dose‐dependent
metabolite–drug
interactions.
Emerging
techniques,
including
single‐cell
artificial
intelligence,
mass
spectrometry
imaging,
are
also
explored
their
potential
enhance
discovery.
emphasizes
metabolomics'
critical
role
advancing
our
understanding
disease
accelerating
targeted
development,
while
acknowledging
current
challenges
field.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Nov. 16, 2024
Abstract
Tryptophan
catabolism
along
the
kynurenine
pathway
(KP)
mediates
key
physiological
functions
ranging
from
immune
tolerance
to
lens
UV
protection,
but
contributory
roles
and
chemical
fates
of
individual
KP
metabolites
are
incompletely
understood.
This
particularly
concerns
first
metabolite,
N-formylkynurenine
(NFK),
canonically
viewed
as
a
transient
precursor
downstream
(KYN).
Here,
we
challenge
that
canon
show
hydrolytic
enzymes
act
rheostat
switching
fate
NFK
between
canonical
novel
non-enzymatic
branch
tryptophan
catabolism.
In
environment
(37°C,
pH
7.4),
deaminated
into
electrophilic
NFK-
carboxyketoalkene
(NFK-CKA),
which
rapidly
(<
2
minutes)
formed
adducts
with
nucleophiles
such
cysteine
glutathione,
intracellular
antioxidants.
Serum
hydrolases
suppressed
deamination
they
hydrolysed
KYN
∼3
times
faster
than
deaminates.
Whilst
did
not
deaminate,
its
product
(KYN-CKA)
reacted
glutathione.
The
new
transformations
yet
be
confirmed
highlight
significance
beyond
hydrolysis
suggests
dominance
over
those
in
environments.
Enzyme
compartmentalisation
abundance
offer
insights
regulation
emerging
contributors
regulation,
protein
modification,
aging
or
neuropathology.
npj Metabolic Health and Disease,
Journal Year:
2024,
Volume and Issue:
2(1)
Published: Oct. 11, 2024
Cardiometabolic
complications
of
obesity
present
a
growing
public
health
concern
and
are
associated
with
poor
outcomes,
mediated
in
part
by
an
increased
risk
for
cardiovascular
disease,
metabolic
dysfunction-associated
fatty
liver
systemic
insulin
resistance.
Recent
studies
support
that
both
resistance
also
aberrant
brain
metabolism
cognitive
impairment
similar
to
what
is
observed
neurodegenerative
diseases.
Central
these
pathological
outcomes
adverse
changes
tissue
glucose
ketone
body
metabolism,
suggesting
regulation
substrate
utilization
could
be
mechanistic
link
between
the
cardiometabolic
progression
decline.
Here,
we
review
physiological
conditions
emphasis
on
therapeutic
potential
bodies
treating
diseases
lead
We
highlight
recent
findings
associations
among
while
providing
theoretical
framework
which
may
promote
positive
preserve
function.
Research Square (Research Square),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Oct. 19, 2023
Abstract
Introduction:
Neurodegenerative
disorders,
characterized
by
progressive
neuronal
loss,
remain
a
significant
clinical
challenge
due
to
their
multifactorial
etiology.
While
numerous
enzymes
have
been
implicated
in
pathogenesis,
there
remains
knowledge
gap
regarding
the
precise
biochemical
roles
of
several
novel
enzyme
targets.
Methods:
This
study
encompassed
multi-pronged
approach,
involving
patient-derived
samples
from
Alzheimer's
and
Parkinson's
cases
(n=156),
an
ALS
mouse
model
(n=50),
CRISPR-Cas9
edited
Huntington's
Disease
zebrafish
(n=100).
Enzyme
activity
assays,
localization
microscopy,
interaction
pathway
analyses
were
conducted.
Results:
Elevated
Aminotransferases
was
observed
78%
compared
controls
(p<0.05).
The
revealed
30%
reduction
motor
neuron
counts
tandem
with
altered
(p<0.01).
successfully
displayed
genetic
markers
post-CRISPR
editing,
indicating
95%
editing
efficiency.
Furthermore,
interactions
between
established
neurodegenerative
pathways
identified.
Conclusion:
Mine
findings
highlight
pivotal
role
targets
offering
potential
avenues
for
early
detection
therapeutic
interventions.
intricate
interplay
these
known
disease
underscores
need
integrated
approach
understand
mechanisms
holistically.
