The selective branch of autophagy that deals with identification, capture and
degradation of protein aggregates is called aggrephagy. In neurodegenration,
essential protein quality control mechanisms fail as the constituent
components also find themselves trapped in the aggregates. Thus, although
cellular aggrephagy has the potential to be upregulated, its dysfunction
further aggravates the pathogenesis.
We have identified a small molecule autophagy modulator, 6-Bio, that shows
clearance of toxic SNCA/α-synuclein (a protein implicated in synucleopathies)
aggregates in yeast and mammalian cell lines. 6-Bio induces autophagy and
dramatically enhances autolysosome formation resulting in SNCA degradation.
Importantly, the neuroprotective function of 6-Bio as envisaged by
immunohistology and behavior analyses in a preclinical model of PD suggests
that it could be a potential therapeutic candidate for protein conformational
disorders.
Figure:
Representative photomicrographs of TH + immunostained DAergic
Placebo control cohort, MPTP-treated (23.4 mg/kg body weight),
6-Bio (5 mg/kg body weight) or both [Prophylaxis
(MPTP+Pro)/Coadministration (MPTP+Co)].
