Serum protein halogenation and nitrosylation: trait of maintained overstimulation of blood phagocytes in sporadic Parkinson’s disease

Abstract

Introduction: Halogenative and nitrosative stress are two types of oxidative stress that have been proposed as pathogenic mechanisms in Parkinson’s disease (PD). They can be caused by overstimulation of phagocytes. This hypothesis discusses serum protein halogenation and nitrosylation as traits of maintained overstimulation of blood phagocytes in sporadic Parkinson’s disease. Hypothesis: I hypothesize that maintained phagocyte overstimulation leads to both halogenative and nitrosative stress in PD, which are present in the serum and cerebrospinal fluid of patients. These types of oxidative stress could modify proteins related to the pathogenesis of PD. Evaluation of hypothesis: It has been detected that the presence of halogenative stress in the serum and, to a lesser extent, cerebrospinal fluid of Parkinsonian patients leads to excess of advanced oxidized protein products. On the other hand, nitrosative stress is also present in serum and cerebrospinal fluid of patients with early PD, characterized by the selective increase of 3-nitrotyrosine proteins other than nitroalbumin and free 3-nitrotyrosine. Nitrosylation stress accompanies modification of the sites of nitrosylation of α-synuclein in these patients, characterized by dominant nitrosylation of tyrosine 125/136 residues. Conclusion: Since metabolism of advanced oxidized protein products and 3-nitrotyrosine proteins has been associated with phagocytic overstimulation, this pathological alteration could play a pathogenic role in sporadic PD. Our observations also lead to the hypothesis that serum level of advanced oxidized protein products is a prognostic marker for PD duration, and these oxidized proteins could participate in neuroinflammation. Besides, the evaluation of nitrosative stress through enhanced levels of 3-nitrotyrosine proteins in serum and cerebrospinal fluid without changes in nitroalbumin, together with the profile of tyrosine nitrosylation of serum α-synuclein characterized by dominant nitrosylation of Tyr125/136, could serve for the diagnosis of sporadic PD. Nitro-α-synuclein is a main component of Lewy bodies, hallmarks of the disease, and serum nitro-α-synuclein could represent a pathogenic factor in PD.