Characterization of a Signalling Pathway Underlying Neuronal Cell Death After Trophic Support Withdrawal Or TNFα Treatment

In the central nervous system, cell death occurs naturally during embryogenesis, as an essential part of neuronal development, and in the adult, during neurodegenerative disorders associated with aging such as Parkinson’s disease (PD), Alzheimer’s disease, Huntington’s disease and amyotrophic lateral sclerosis (1,2, 3). Among these disorders, PD is characterized by the progressive loss of dopaminergic neurons in the nigrostriatal system. Little is known about the mechanisms that lead to the death of these neurons (4). However, data obtained in post-mortem brain from patients with PD suggest that the nigrostriatal dopaminergic neurons die by apoptosis, that may be activated by the cytokine tumor necrosis factor a (TNF α): 1) Ultrastructural analysis of dopaminergic neurons in the substantia nigra (SN) of patients with PD revealed characteristics of apoptosis and autophagic degeneration (5). 2) Activated microglial cells have been observed in the SN of parkinsonian patients. Some of these cells are immunoreactive for the cytokine TNF α and are localized near the dopaminergic neurons that degenerate during the disorder. Interestingly TNF α receptors have been detected on these neurons (6).