[Rhonda]: In the case of mitophagy here, it's
also it plays an important role in the prevention
of neurodegenerative diseases.
Correct?
[Dr. Kroemer]: Yes.
So, most known neurodegenerative diseases
are either caused by the aggregation of poorly
built protein cell that somehow create protein
aggregates that are toxic for the cell.
Or they can also be caused by septal deficiencies
in the autophagic and lysosomal machineries
that lead to the accumulation of unfolded
proteins at the end.
And so, either the excessive production of
unfolded proteins or their reduced removal
causes to a slow accumulation of these toxic
protein aggregates.
Remember that neurodegenerative diseases are
slow processes in most cases that manifests
with old age.
And so, one strategy to treat neurodegeneration,
at least theoretically, is to increase autophagic
turnover.
And so, one technique is actually then to
stimulate general autophagy by increasing
the demand, by starvation, or by biochemical
trickster that substitute for starvation,
and to reduce the protein aggregates that
are the cause of the disease.
[Rhonda]: So these protein aggregates like
amyloid beta plaques in Alzheimer's disease
or alpha-synuclein in Parkinson's disease.
So, basically, the clearing out of those protein
aggregates obviously would play an important
role not only in prevention but presumably
also, to some degree, in help with the treatment.
Of course, that's you know, an speculation,
but...
And then the mitochondria, the one I was thinking
about with mitophagy, was the role, at least
some of the proteins that are involved in
that, like, the PINK/Parkin, and how they
seem to be important for Parkinson's disease.
Is that accurate?
[Dr. Kroemer]: Yeah.
So the PINK/Parkin pathway is one pathway
among others, that allows for marking mitochondria
that are damaged for destruction.
And so, inhibition of this pathway leads to
the accumulation of malfunctioning mitochondria
with major consequences for the cell that
harbours cells' mitochondria because all of
a sudden bioenergetic metabolism becomes inefficient,
reactive oxygen species are produced, and
as you know, mitochondria are latent bombs
in the sense that they enclose potentially
dangerous proteins that once released will
activate the apoptotic machinery and cause
cellular suicide.
[Rhonda]: Yeah.
