HtrA2/0mi-immunoreactive intraneuronal inclusions in the anterior horn of patients with sporadic and Cu/Zn superoxide dismutase (SOD1) mutant amyotrophic lateral sclerosis

摘要

Aims: HtrA2/0mi is a mitochondrial serine protease that promotes the apoptotic processes, but the relationship between HtrA2/0mi and amyotrophic lateral sclerosis (ALS) is still unknown. The purpose of the present study was to determine whether abnormal expression of HtrA2/ Omi occurs in patients with ALS. Methods: We prepared autopsied spinal cord tissues from 7 control subjects, 11 patients with sporadic ALS (SALS) and 4 patients with Cu/Zn superoxide dismutase (SODl)-related familial ALS (FALS). We then performed immunohistochemical studies on HtrA2/0mi using formalin-fixed, paraffin-embedded sections from all of the cases. Results: In the control subjects, the anterior horn cells were mildly to moderately immunostained with HtrA2/0mi. In the patients withSALS, strong HtrA2/0mi irnmunoreactivity was found in some skein-like inclusions and round hyaline inclusions as well as many spheroids, but Bunina bodies were immu-nonegative for HtrA2/0mi. In the patients with SOD1-related FALS, Lewy body-like hyaline inclusions were observed in three cases and conglomerate inclusions were observed in the remaining case, and both types of inclusions were intensely immunopositive for HtrA2/0mi. Conclusions: These results suggest that abnormal accumulations of HtrA2/0mi may occur in several types of motor neuronal inclusions in the anterior horn from SALS and SODl-linked FALS cases, and that HtrA2/0mi may be associated with the pathogenesis of both types of ALS.