HSP27 but not HSP70 has a potent protective effect against α‐synuclein‐induced cell death in mammalian neuronal cells

α‐Synuclein is a neuronally expressed protein which is mutated in familial Parkinson's disease. We have previously shown that disease‐associated mutants of α‐synuclein cause enhanced neuronal cell death in response to a variety of stimuli, whereas wild‐type α‐synuclein has a protective effect against some stimuli, whilst enhancing the death response to others. We demonstrate, for the first time, that over‐expression of the heat shock protein HSP27 has a potent protective anti‐apoptotic effect against the damaging effects of wild‐type and particularly of mutant α‐synuclein. In contrast, HSP70 has some protective effect against the damaging effect of the wild‐type protein, but has no effect against the mutant proteins, whilst HSP56 has no protective effect in this system. Our results indicate that disease‐associated mutants of α‐synuclein enhance its death‐inducing properties and lead to increased apoptosis, which can be mitigated by either the use of specific caspase inhibitors or HSP27 over‐expression. This potent protective effect of HSP27 against the mutant and wild‐type proteins may be of potential therapeutic importance.

Duke Scholars

Author Martin D. Smith Marine Science and Conservation