Human neurodegenerative diseases are accompanied by accumulation of heavily oxidized and aggregated proteins. However, the exact molecular reason is not fully elucidated yet. Insufficient cellular protein quality control is thought to play an important role in accumulating covalently oxidized misfolded proteins. Pharmacologically active polyphenols and their derivatives exhibit potential for preventive and therapeutic purposes against protein aggregation during neurodegeneration. Although these compounds act on various biochemical pathways, their role in stabilizing the protein degradation machinery at different stages may be an attractive therapeutical strategy to halt the accumulation of misfolded proteins. This review evaluates and discusses the existing scientific literature on the effect of polyphenols on three major protein degradation pathways: chaperone-mediated autophagy, the proteasome and macroautophagy. The results of these studies demonstrate that phenolic compounds are able to influence the major protein degradation pathways at different levels.
Keywords: chaperone-mediated autophagy; macroautophagy; neuroprotection; proteasome; protein degradation; protein oxidation; proteostasis.