Fas and Fas-L expression in Huntington's disease and Parkinson's disease

The Fas/Fas-L signalling system plays a role in the control of cell death a nd the survival of lymphocytes, in the regulation of the immune system, and in the progression of autoimmune diseases. Studies in the nervous system h ave shown Fas/Fas-L activation in multiple sclerosis and in various paradig ms leading to neuronal death. Enhanced Fas and Fas-L expression has also be en documented in astrocytomas and glioma cell lines. However, little is kno wn about the possible implication of Fas/Fas-L signals in primary human neu rodegenerative diseases. In an attempt to gain understanding of the mechani sms commanding cell death and neurone loss in Huntington's disease (HD) and Parkinson's disease (PD), Fas and Fas-L expression has been examined in th e brains of patients with HD and PD with Western blotting and immunohistoch emistry. Fas and Fas-L expression levels are reduced in the caudate and put amen, but not in the parietal cortex, in HD, as revealed in Western blots. Moreover, Fas and Fas-L immunoreactivity is reduced in striatal neurones in HD. Fas and Fas-L immunoreactivity is also decreased in neurones of the su bstantia nigra pars compacta in PD. Reduced Fas and Fas-L expression is obs erved equally in Lewy body-bearing and non-Lewy body-bearing neurones. Yet increased Fas and Fas-L immunoreactivity occurs in normal astrocytes in con trol brains and in reactive astrocytes in diseased brains. The meaning of i ncreased Fas and Fas-L expression in astrocytes is still unclear. However, the present results suggest that Fas/Fas-L signals are minimized in sensiti ve neurones in HD and PD.