Protein quality control during aging involves recruitment of the macroautophagy pathway by BAG3

The Hsc/Hsp70 co-chaperones of the BAG (Bcl-2-associated athanogene) protein family are modulators of protein quality control. We examined the specific roles of BAG1 and BAG3 in protein degradation during the aging process. We show that BAG1 and BAG3 regulate proteasomal and macroautophagic pathways, respectively, for the degradation of polyubiquitinated proteins. Moreover, using models of cellular aging, we find that a switch from BAG1 to BAG3 determines that aged cells use more intensively the macroautophagic system for turnover of polyubiquitinated proteins. This increased macroautophagic flux is regulated by BAG3 in concert with the ubiquitin-binding protein p62/SQSTM1. The BAG3/BAG1 ratio is also elevated in neurons during aging of the rodent brain, where, consistent with a higher macroautophagy activity, we find increased levels of the autophagosomal marker LC3-II as well as a higher cathepsin activity. We conclude that the BAG3-mediated recruitment of the macroautophagy pathway is an important adaptation of the protein quality control system to maintain protein homeostasis in the presence of an enhanced pro-oxidant and aggregation-prone milieu characteristic of aging

The Effect of Polyphenols on Protein Degradation Pathways: Implications for Neuroprotection

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

The effect of polyphenols on protein degradation pathways : implications for neuroprotection

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

The Effect of Polyphenols on Protein Degradation Pathways: Implications for Neuroprotection

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

Probing the Role of Cysteine Thiyl Radicals in Biology: Eminently Dangerous, Difficult to Scavenge

Thiyl radicals are exceptionally interesting reactive sulfur species (RSS), but rather rarely considered in a biological or medical context. We here review the reactivity of protein thiyl radicals in aqueous and lipid phases and provide an overview of their most relevant reaction partners in biological systems. We deduce that polyunsaturated fatty acids (PUFAs) are their preferred reaction substrates in lipid phases, whereas protein side chains arguably prevail in aqueous phases. In both cellular compartments, a single, dominating thiyl radical-specific antioxidant does not seem to exist. This conclusion is rationalized by the high reaction rate constants of thiyl radicals with several highly concentrated substrates in the cell, precluding effective interception by antioxidants, especially in lipid bilayers. The intractable reactivity of thiyl radicals may account for a series of long-standing, but still startling biochemical observations surrounding the amino acid cysteine: (i) its global underrepresentation on protein surfaces, (ii) its selective avoidance in aerobic lipid bilayers, especially the inner mitochondrial membrane, (iii) the inverse correlation between cysteine usage and longevity in animals, (iv) the mitochondrial synthesis and translational incorporation of cysteine persulfide, and potentially (v) the ex post introduction of selenocysteine into the genetic code

Stress associated epigenetic changes in saliva (STEPS)

The aim of this study is to investigate the influence of an acute laboratory psychosocial stressor (Trier Social Stress Test (TSST)) (Kirschbaum et al., 1993) on microRNA (miRNA) and messengerRNA (mRNA) levels in saliva. The experimental study is a conceptual replication of Jurkiewicz et al. (2021) which will take place at the MSH Medical School Hamburg (MSH), Germany. Literature: Jurkiewicz, M. M., Mueller-Alcazar, A., Moser, D. A., Jayatilaka, I., Mikhailik, A., Ferri, J., Fogelman, N., & Canli, T. (2021). Integrated microRNA and mRNA gene expression in peripheral blood mononuclear cells in response to acute psychosocial stress: a repeated-measures within-subject pilot study. BMC Research Notes, 14(1), 222. https://doi.org/10.1186/s13104-021-05635-3 Kirschbaum, C., Pirke, K.M, Hellhammer, D.H. The ‘Trier Social Stress Test’—a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology. 1993;28:76–81