Biotransformation of nitric oxide in the cerebrospinal fluid of amyotrophic lateral sclerosis patients

Abstract

Recent findings indicate that nitric oxide (NO•) over-production might be an important factor in thepathogenesis of sporadic amyotrophic lateral sclerosis (SALS). We measured significantly higherconcentrations of uric acid and thiol group-containing molecules (R–SH groups) in thecerebrospinal fluid (CSF) from SALS patients compared to controls. The above factors, togetherwith a slightly increased free iron concentration found in the CSF, favour conditions necessary forthe formation of the dinitrosyl iron complex, capable of NO•bio-transformation. Thus, weperformed ex vivosaturation of CSF (from both SALS patients and controls) with NO•. A decreasein the level of R–SH was found. This was more pronounced in the CSF from SALS patients. In theCSF from SALS patients the production of nitrite and hydroxylamine was greater than that observedin the CSF from controls. Moreover, we also found increased Cu,Zn-SOD activity in the CSF fromSALS patients (when compared to control subjects) but no activity corresponding to Mn-SOD inany CSF samples. As Cu,Zn-SOD can react with nitroxyl forming NO•, the conditions for a closed,but continuous, loop of NO•biotransformation are present in the CSF of ALS patients.