Impact of glucocorticoids and chronic stress on progression of Parkinson's disease.

Parkinson's disease, a chronic progressive neurodegenerative disorder, has a mainly unknown multifactorial etiology. It is characterized by progressive degeneration of dopaminergic neurons. Chronic stress, a condition mediated by elevated concentrations of glucocorticoids over an extended period of time, has been shown to be unfavourable for neurons and to cause damage and neuronal loss in certain brain areas. Glucocorticoids are most probably not toxic in a direct manner, but can make neuronal damage through several potential indirect mechanisms in combination with other destructive factors. We postulate that chronic stress will have a harmful effect on patients with Parkinson's disease, facilitating neuronal degeneration and accelerating progression of clinical manifestations. The damaging impact on neurons will not be because of direct cytotoxicity, but by putting them into an energetically unfavourable condition, in which they will be more sensitive to destructive factors caused by the primary process. Possible mechanisms include elevation of excitatory amino acid concentration, which are excitotoxic, disruption of calcium homeostasis, metabolic disturbance or impairment of neurogenesis. This could have significant implications for patients with Parkinson's disease and chronic stress, or patients with glucocorticoid treatment for various immunopathological diseases, as well as patients with abnormal secretion of glucocorticoids such as in Cushing's syndrome. If confirmed, this hypothesis would represent a valuable advancement in care of patients with Parkinson's disease.