AUTHOR=Friesen Erik L. , Zhang Yu Tong , Earnshaw Rebecca , De Snoo Mitch L. , O’Hara Darren M. , Agapova Victoria , Chau Hien , Ngana Sophie , Chen Kevin S. , Kalia Lorraine V. , Kalia Suneil K. 

TITLE=BAG5 Promotes Alpha-Synuclein Oligomer Formation and Functionally Interacts With the Autophagy Adaptor Protein p62

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 8 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.00716

DOI=10.3389/fcell.2020.00716

ISSN=2296-634X

ABSTRACT=Molecular chaperones are critical to maintaining intracellular proteostasis and have been shown to have a protective role against alpha-synuclein mediated toxicity. Co-chaperone proteins regulate the activity of molecular chaperones and connect the chaperone network to protein degradation and cell death pathways. Bcl-2 associated athanogene 5 (BAG5) is a co-chaperone that modulates proteostasis by inhibiting the activity of Hsp70 and several E3 ubiquitin ligases, resulting in enhanced neurodegeneration in models of Parkinson’s disease (PD). Here we identify a novel interaction between BAG5 and p62/sequestosome-1 (SQSTM1), suggesting that BAG5 may bridge the chaperone network to autophagy-mediated protein degradation. We found that BAG5 enhanced the formation of pathogenic alpha-synuclein oligomers and regulated the levels and subcellular distribution of p62. These results extend the role of BAG5 in alpha-synuclein processing and intracellular proteostasis.