Spinocerebellar ataxia type 3 (SCA3), caused by the abnormal expansion of polyglutamine (polyQ) in the ataxin-3 protein, is one of the inherited polyQ neurodegenerative diseases that share similar genetic and molecular features. Mutant polyQ-expanded ataxin-3 protein is prone to aggregation in affected neurons and is predominantly degraded by autophagy, which is beneficial for neurodegenerative disease treatment. Not only does mutant polyQ-expanded ataxin-3 increase susceptibility to oxidative cytotoxicity, but it also hampers antioxidant potency in neuronal cells. Nuclear factor erythroid-derived 2-like 2 (Nrf2), a master transcription factor that controls antioxidant and detoxification gene expression, plays a crucial role in neuroprotection in SCA3 and other neurodegenerative diseases. The present data showed that treatment with erinacine A-enriched Hericium erinaceus mycelium ethanol extract (HEME) extended longevity and improved locomotor activity in ELAV-SCA3tr-Q78 transgenic Drosophila. Moreover, HEME treatment enhanced antioxidant potency and autophagy, which, in turn, corrected levels of mutant polyQ-expanded ataxin-3 and restrained protein aggregation in both cell and Drosophila models of SCA3. Markedly, HEME increased the activation of Nrf2. Silencing Nrf2 protein expression negated most of the promising effects of HEME on SK-N-SH-MJD78 cells, highlighting the critical role of increased Nrf2 activation in the efficacy of HEME treatment. These findings suggest that HEME has therapeutic potential in SCA3 by enhancing autophagic and Nrf2-mediated antioxidant pathways, which may also influence neurodegenerative progression in other polyQ diseases.

Muscle atrophy, through several pathways including increased protein catabolism, leads to adverse effects in cachexia induced by cancer and chemotherapy. Perch essence (PE) is a perch extract rich in branched-chain amino acids and peptides. The present study initially investigated the effects of PE supplementation on muscle atrophy in a mouse model of cancer cachexia induced by C26 cancer cells and compared these effects with those of tryptone. Compared with the tumor-only group, we found that PE supplementation significantly improved body weight, muscle mass, maximum limb grip strength (MLGS), and myosin heavy chain expression in the muscles of tumor-bearing mice. PE also significantly inhibited the expression of factors related to protein degradation, oxidative stress, and inflammation, while enhancing the expression of antioxidant enzymes in tumor-bearing mice. These effects of PE were associated with an increased expression of phosphorylated Akt and forkhead box protein O1, along with a reduced expression of phosphorylated nuclear factor-κB p65 in the muscles of tumor-bearing mice. Furthermore, PE similarly increased MLGS and attenuated muscle atrophy in mice exposed to cisplatin by inhibiting protein degradation. All the therapeutic effects of PE supplementation mentioned above were generally greater than those of tryptone supplementation. These results suggest the potential of PE in protecting against muscle atrophy induced by tumors or chemotherapy.