HspB5/αB-Crystallin in the Brain

Abstract

Many organs including the brain exhibit powerful endogenous cytopro-tective mechanisms to survive recurrent cellular stress events, i.e. the development of stress tolerance. Investigation of the molecular mechanisms underlying this neu-roprotective phenomenon is of special interest since it may provide the basis to develop new therapeutic strategies for the treatment of neurological diseases. One important mechanism is the upregulation of heat shock proteins. Here, we will review the neuroprotective potential of HspB5/αB-crystallin. HspB5 is expressed in glia as well as in neurons and upregulated in certain cell types or subset of cells at pathophysiological conditions. HspB5 is found to be associated with the disease-causing pathological protein aggregates, such as amyloid plaques in Alzheimer's disease or Rosenthal fi bers in Alexander disease. One possible function of HspB5 is to counteract the aggregation process leading to increased cell survival. However, HspB5 may act additionally via its non-chaperone functions, such as anti-infl amma-tory, anti-apoptotic properties or association with cytoskeletal proteins infl uencing fi lament assembly. The cytoprotective activity of HspB5 is regulated by phosphory-lation. Interestingly, in neurons HspB5 is recruited to axons and dendrites by phos-phorylation, however, to this end little is known about the molecular targets of phosphoHspB5 in neurons. Identifying the impact of phosphorylation of HspB5 in glia and neurons and the targets of HspB5 may be useful to develop new therapeutic strategies for neurological diseases.