Abstract: Amyloid protein aggregation plays a major role in multiple neurodegenerative diseases and is likely the primary driving force for the progression of most of these diseases. Multiple recent studies have highlighted that the DNAJ homolog subfamily B member 6 (DNAJB6) chaperone is particularly interesting, when it comes to preventing amyloidogenic proteins from aggregating. It has been shown that DNAJB6 can prevent the aggregation of polyglutamine-expanded proteins in models of Huntington’s disease. Likewise, it can suppress aggregation of α-synuclein in models of Parkinson’s disease and other synucleinopathies. Finally, it has been shown that DNAJB6 can block aggregation of multiple additional amyloid proteins involved in Alzheimer’s disease and other tauopathies as well. We believe there is yet much to learn about the protective role of DNAJB6 in the brain, but this focused review summarizes, what we know so far of this chaperone. It describes the biological role of DNAJB6 in the brain and its interaction with Hsp70, with particular emphasis on the studies that show its ability to prevent amyloid protein aggregation in vitro and in vivo. Moreover, recent work on dysregulation of the expression of DNAJB6 in brain clinical tissue is discussed. Finally, we discuss potential therapeutic perspectives as we believe this protein is a promising druggable target.

Key words: aggregation, chaperones, clinical tissues, DNAJB6, human brain, neurodegeneration, neurodegenerative diseasestherapeutic target