> Be hungry... be healthy... be hungrier... be healthier...
Good advice. I try to fast on Sundays.
The formation of peripheral myelin protein 22 aggregates is hindered
by the enhancement of autophagy and expression of cytoplasmic
chaperones.
The ac***ulation of misfolded proteins is associated with various
neurodegenerative conditions. Peripheral myelin protein 22 (PMP22) is
a hereditary neuropathy-linked, short-lived molecule that forms
aggresomes when the proteasome is inhibited or the protein is mutated.
We previously showed that the removal of pre-existing PMP22 aggregates
is assisted by autophagy. Here we examined whether the ac***ulation of
such aggregates could be suppressed by experimental induction of
autophagy and/or chaperones. Enhancement of autophagy during
proteasome inhibition hinders protein aggregate formation and
correlates with a reduction in ac***ulated proteasome substrates.
Conversely, simultaneous inhibition of autophagy and the proteasome
augments the formation of aggregates. An increase of heat shock
protein levels by geldanamycin treatment or heat shock preconditioning
similarly hampers aggresome formation. The beneficial effects of
autophagy and chaperones in preventing the ac***ulation of misfolded
PMP22 are additive and provide a potential avenue for therapeutic
approaches in hereditary neuropathies linked to PMP22 mutations. PMID:
17174099
