title: Increased mitochondrial oxidative damage and oxidative DNA damage contributes to the neurodegenerative process in sporadic amyotrophic lateral sclerosis.
abstract: To investigate the possibility that mitochondrial oxidative damage or oxidative DNA damage or both contribute to the neurodegenerative process of sporadic amyotrophic lateral sclerosis (sALS), this study used high-performance liquid chromatography with an electrochemical detector to measure the concentrations of the reduced and oxidized forms of coenzyme Q10 (CoQ10) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the cerebrospinal fluid (CSF) of 17 patients with sALS and 17 age-matched controls with no neurological diseases. The percentage of oxidized CoQ10 in the CSF of sALS patients was greater than that in the CSF of controls (p<0.002) and was negatively correlated with the duration of illness (rho=-0.61, p<0.01). The concentration of 8-OHdG in the CSF of sALS patients was greater than that in the CSF of controls (p<0.005) and was positively correlated with the duration of illness (rho=0.53, p<0.005). The percentage of oxidized CoQ10 was correlated with the concentrations of 8-OHdG in the CSF of sALS patients (rho=-0.53, p<0.05). These results suggest that both mitochondrial oxidative damage and oxidative DNA damage play important roles in the pathogenesis of sporadic amyotrophic lateral sclerosis.
authors.affiliation: Department of Neurology, Iwate Prefectural Ninohe Hospital, Ninohe, Iwate, Japan. takahm@nyc.odn.ne.jp
authors.forename: Takahiko
authors.initials: T
authors.lastname: Murata
authors.forename: Chigumi
authors.initials: C
authors.lastname: Ohtsuka
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Terayama
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid / Q000378:metabolism*; D017209:Apoptosis; D016022:Case-Control Studies; D002845:Chromatography / Q000379:methods; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000737:chemistry; D006801:Humans; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D019636:Neurodegenerative Diseases / Q000134:cerebrospinal fluid / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism; D013997:Time Factors
chemical_list: D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D010100:Oxygen