Moreover, the autophagic proteins, autophagy-related gene (Atg) protein (ATG)-7, ATG-12, ATG16L2 and autophagosomal microtubule-associated protein light chain 3 (LC3) were significantly increased in MJD brains relative to controls, while beclin-1 levels were reduced in MJD patients.
The overexpression of beclin-1 on MJD fibroblasts reverted partially autophagy impairment by increasing the autophagic flux but failed to increase the levels of autophagosome production.
These data demonstrate that autophagy is a key degradation pathway, with beclin-1 playing a significant role in alleviating Machado-Joseph disease pathogenesis.