Caspase activities and tumor necrosis factor receptor R1 (p55) level are elevated in the substantia nigra from Parkinsonian brain

The activities of caspase-1 and caspase-3 were measured by use of fluoropep tides as substrates for the first time in the brain (substantia nigra, caud ate nucleus, putamen, cerebellum, and frontal cortex) from control and park insonian patients. The activities of caspases in the brain were significant ly higher in the substantia nigra from parkinsonian patients than those in the brain from control patients (p < 0.01). However, the activities of casp ases in the caudate nucleus, putamen, cerebellum, and frontal cortex showed no significant difference between parkinsonian and control patients. The t umor necrosis factor (TNF) receptor R1 (TNF-R1, p55) level was also elevate d in the substantia nigra of the parkinsonian brain in comparison with that of controls (p < 0.05). Since both caspases and TNF-R1 may play important roles in apoptotic cell death through! TNF-alpha-induced signaling pathway, our present data suggest the presence of a proapoptotic environment in the substantia nigra of parkinsonian brain, probably inducing vulnerability of neurons and glias towards a variety of noxious factors.