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Sporadic inclusion-body myositis: A degenerative muscle disease associated with aging, impaired muscle protein homeostasis and abnormal mitophagy.
[inclusion body myositis]
Sporadic
inclusion-body
myositis
(
s-
IBM
)
is
the
most
common
degenerative
muscle
disease
in
which
aging
appears
to
be
a
key
risk
factor
.
In
this
review
we
focus
on
several
cellular
molecular
mechanisms
responsible
for
multiprotein
aggregation
and
accumulations
within
s-
IBM
muscle
fibers
,
and
their
possible
consequences
.
Those
include
mechanisms
leading
to
:
a
)
accumulation
in
the
form
of
aggregates
within
the
muscle
fibers
,
of
several
proteins
,
including
amyloid-β
42
and
its
oligomers
,
and
phosphorylated
tau
in
the
form
of
paired
helical
filaments
,
and
we
consider
their
putative
detrimental
influence
;
and
b
)
protein
misfolding
and
aggregation
,
including
evidence
of
abnormal
myoproteostasis
,
such
as
increased
protein
transcription
,
inadequate
protein
disposal
,
and
abnormal
posttranslational
modifications
of
proteins
.
Pathogenic
importance
of
our
recently
demonstrated
abnormal
mitophagy
is
also
discussed
.
The
intriguing
phenotypic
similarities
between
s-
IBM
muscle
fibers
and
the
brains
of
Alzheimer
and
Parkinson
's
disease
patients
,
the
two
most
common
neurodegenerative
diseases
associated
with
aging
,
are
also
discussed
.
This
article
is
part
of
a
Special
Issue
entitled
:
Neuromuscular
Diseases
:
Pathology
and
Molecular
Pathogenesis
.
Diseases
Validation
Diseases presenting
"sporadic inclusion-body myositis"
symptom
focal myositis
inclusion body myositis
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