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 and the survival of lymphocytes, in the regulation of the immune system, and in the progression of autoimmune diseases. Studies in the nervous system have shown Fas/Fas-L activation in multiple sclerosis and in various paradigms leading to neuronal death. Enhanced Fas and Fas-L expression has also been documented in astrocytomas and glioma cell lines. However, little is known about the possible implication of Fas/Fas-L signals in primary human neurodegenerative diseases. In an attempt to gain understanding of the mechanisms 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 the brains of patients with HD and PD with Western blotting and immunohistochemistry. Fas and Fas-L expression levels are reduced in the caudate and putamen, 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 substantia nigra pars compacta in PD. Reduced Fas and Fas-L expression is observed equally in Lewy body-bearing and non-Lewy body-bearing neurones. Yet increased Fas and Fas-L immunoreactivity occurs in normal astrocytes in control brains and in reactive astrocytes in diseased brains. The meaning of increased Fas and Fas-L expression in astrocytes is still unclear. However, the present results suggest that Fas/Fas-L signals are minimized in sensitive neurones in HD and PD.
Ferrer
I
I
Unitat de Neuropatologia, Servei d'Anatomia Patològica, Hospital Princeps d'Espanya, Barcelona, Spain. iferrer@sakma.es
Blanco
R
R
Cutillas
B
B
Ambrosio
S
S
D000368:Aged; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor