Abstract
The small heat shock protein αB-crystallin (HspB5) is known to be overexpressed in several neurodegenerative disorders. In familial amyloidotic polyneuropathy (FAP), a neurodegenerative disorder characterized by extracellular deposition of mutated transthyretin (TTR), activation of heat shock factor 1 -HSF1- by extracellular TTR deposition has been shown as well as induction of the expression of heat shock proteins, HSP27 and HSP70. Here we investigate the expression of αB-crystallin in FAP. We first detected αB-crystallin in aggregates extracted from tissues of both FAP patients and transgenic mice for the human V30M mutant TTR; however, subsequent studies by confocal fluorescence microscopy did not confirm the association of αB-crystallin with TTR aggregates; thus the presence of αB-crystallin in aggregate extracts might derive from the extraction procedure. Increased levels of αB-crystallin were observed by immunohistochemistry in human FAP skin, as compared to normal skin. Furthermore, skin, stomach and dorsal root ganglia from V30M transgenic mice showed increased expression of αB-crystallin as compared to controls without deposition. A human neuroblastoma cell line incubated with TTR aggregates displayed increased expression of αB-crystallin. Overall, these results show that extracellular TTR deposits induce an intracellular response of αB-crystallin. This small heat shock protein (HSP), which is important for anti-apoptotic and chaperone properties, may have a protective role in FAP.