Parkinson's disease: biology and aetiology.

The cause of dopamine cell death, thought to be the primary neurocytologic defect in idiopathic Parkinson's disease, remains unknown. Mitochondrial oxidative dysfunction causes premature cell death, and may be linked to accelerated apoptosis, excessive free and toxic radicals, deficient neurotrophic factors or combinations of these detrimental factors. Neurochemical imbalances result both in the substantia nigra and neostriatum, resulting in compensatory mechanisms that make this chronic neurodegenerative disease difficult to evaluate. Acute parkinsonism models have limitations when compared with chronic disease states, and caution should be present when comparing 'parkinsonism' data with human disease. Better understanding of classical neurotransmitters, neuroactive peptides and neurotrophic factors, will hopefully lead to more rational treatment approaches, cellular support strategies, and an understanding of the causes of this disease. Glial derived neurotrophic factor looks the most promising neurotrophic candidate so far tested in culture and in vivo. The result of clinical trials utilizing neurotrophic factors, both as mesencephalic implant support strategies and as definitive treatment of idiopathic Parkinson's disease, are awaited with cautious optimism.