Nigral depigmentation reflects monoamine exhaustion as initial step to Parkinson's disease

This hypothesis discusses exposure and response to various stressors as cause for chronic neurodegeneration. Predisposing genetic and environmental factors in conjunction with exposure to exogenous and endogenous toxins cause stress, which consumes dopamine and related biogenic amines. To compensate monoamine exhaustion, conversion of endogenous levodopa to dopamine by tyrosine hydroxylase is up regulated. Concomitantly, tyrosine mediated levodopa degradation to dopaquinone is reduced. Dopaquinone is the essential precursor of neuromelanin. Its deficiency may cause irreversible nigral fading as initial feature of Parkinson's disease.