Anatomical and histological studies have established the existence of selective regional vulnerability to neurodegeneration and cell death. For example, the dopaminergic neurons in the substantia nigra are selectively injured in Parkinson disease, whereas motor neurons in the spinal cord are selectively lost in ALS, and loss of cholinergic neurons frequently occurs in the forebrain of individuals with Alzheimer disease. Despite this regional sensitivity, oxidative processes may represent a specific and selective unifying mechanism for neurodegeneration. Several aspects of this working hypothesis are evident in Parkinson disease and ALS