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Staines DR: Is Parkinson's disease an autoimmune disorder of endogenous vasoactive neuropeptides?. Med Hypotheses. 2007;69(6):1208-11. Epub 2007 Jun 11.
Parkinson's disease (PD) is a motor disease including disorders of mobility, fine tremor, rigidity and posture caused by a relentless deterioration of dopaminergic cells in the substantia nigra (SN). Disorders of affect and a range of other symptoms including fatigue, cognitive dysfunction and mental confusion, sleep disorder and addictions are also seen as other CNS sites are also affected. Idiopathic and genetic causes together with inflammatory and degenerative disorders of ageing have been postulated as contributing to PD. Autoimmunity affecting certain vasoactive neuropeptides (VNs) has been postulated as contributing to certain fatigue-related conditions in humans and may be consistent with compromise of receptors associated with VNs and including receptors for vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP). Pro-inflammatory responses are seen in PD patients consistent with apoptotic neurodegeneration. Involvement of the Th1 directed cytokine interferon-gamma has been demonstrated and Th2 directed cytokines such as IL-10 protect against inflammation-mediated degeneration of dopaminergic neurons in the SN. Nitric-oxide dysregulation is also postulated in PD by fostering dopamine depletion via nitric-oxide synthase (iNOS). Both PACAP and VIP have neuroprotective effects in PD models by inhibiting the production of inflammatory mediators. PACAP specifically protects against the neurotoxicity induced by rotenone as well as protecting against oxidative stress-induced apoptosis. These findings suggest that a defect in VN function may act adversely on SN cells and hence contribute to a clinical presentation consistent with PD. The conclusion drawn from these findings is that PD may be an autoimmune disorder of VNs, specifically PACAP and VIP. Possibly unusual or anatomically specific receptors for these VNs may be involved. If proven, this hypothesis would have significant implications for immunological and pharmacological treatment and prevention of PD. |
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