HSP27 and cell survival in neurones

Abstract

Although the majority of studies on the protective effect of individual hsps have concentrated on the major inducible heat shock protein Hsp70, a variety of evidence suggests that the small heat shock protein Hsp27 may have a more potent protective effect in the nervous system. Thus, for example, in cultured neurones over-expression of Hsp70 can protect against subsequent exposure to thermal or ischaemic stress but not against exposure to some other stressful stimuli, whereas over-expression of Hsp27 protects against a variety of stresses. Similarly, although transgenic animals over-expressing Hsp70 are protected against cardiac ischaemia, more equivocal results have been obtained in terms of their protection against cerebral ischaemia and other stresses to the nervous system. In contrast, transgenic animals over-expressing Hsp27 have recently been shown to show neuroprotection as well as being protected against cardiac ischaemia. Recent findings have also implicated Hsp27 and related proteins in human disease. Thus, it has been demonstrated that mutation of either Hsp27 or the related protein hsp22 can be observed in specific families with hereditary motor neuropathy caused by premature axonal loss, possibly due to neuronal death and subsequent degeneration. Moreover, the mutations are associated with a reduced ability to promote neuronal survival compared to the wild type protein. Hence, Hsp27 appears to be a potent protective factor for neuronal cells whose mutation results in neuronal cell death and disease, whilst enhanced expression of the wild type protein may be a therapeutic option for human diseases involving excessive neuronal cell death.