HspB5/αB-Crystallin in the Brain

Abstract

Many organs including the brain exhibit powerful endogenous cytoprotective mechanisms to survive recurrent cellular stress events, i.e. the development of stress tolerance. Investigation of the molecular mechanisms underlying this neuroprotective 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 diseasecausing 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 ammatory, anti-apoptotic properties or association with cytoskeletal proteins infl uencing fi lament assembly. The cytoprotective activity of HspB5 is regulated by phosphorylation. Interestingly, in neurons HspB5 is recruited to axons and dendrites by phosphorylation, 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.

Differentiation Drives Widespread Rewiring of the Neural Stem Cell Chaperone Network

“…Of note, TRiC is essential and still present in differentiated cells, albeit at much reduced levels (e.g., Figure S4F for higher sensitivity imaging). In contrast to TRiC, HspB5 was undetectable in NSPCs but highly expressed in differentiated cells, including neurons, where it localized to a range of subcellular structures (from diffuse to punctate) (Figures 4D, 4E, and S4G; as also previously reported Golenhofen and Bartelt-Kirbach, 2015).…”

“…These experiments indicate that some mammalian sHSPs induced during NSPC differentiation have the ability to promote spatial sequestration of misfolded proteins into PQC inclusions. Of note, HspB5, which promotes sequestration and is strongly induced upon NSPC differentiation, has been linked to HD pathology and associates with Alzheimer disease fibers (Golenhofen and Bartelt-Kirbach, 2015;Oliveira et al, 2016).…”

Differentiation drives widespread rewiring of the neural stem cell chaperone network

“…Figure S4F for higher sensitivity imaging). In contrast to TRiC, HspB5 was undetectable in NSPCs but highly expressed in differentiated cells, including neurons, where it localized to a range of subcellular structures (from diffuse to punctate) (Figures 4D-E, S4G; as also previously reported (Golenhofen and Bartelt-Kirbach, 2015)).…”

“…These experiments indicate that some mammalian sHSPs induced during NSPC differentiation have the ability to promote spatial sequestration of misfolded proteins into PQC inclusions. Of note, HspB5, which promotes sequestration and is strongly induced upon NSPC differentiation, has been linked to HD pathology and associates with Alzheimer Disease’ fibers (Golenhofen and Bartelt-Kirbach, 2015; Oliveira et al, 2016).…”

αB-crystallin as a promising target in pathological conditions – A review

“…Its expression was found in glia and neurons, and its overexpression was detected in certain cell types at pathophysiological conditions. αB-crystallin is said to be associated with the disease-causing protein aggregates, thus its connection with such neurological disturbances as anaplastic astrocytoma, Parkinson disease, aging deficits in the peripheral nervous system and multiple sclerosis [71][72][73][74][75].…”