Mitochondria in neurodegenerative disorders: regulation of the redox state and death signaling leading to neuronal death and survival.

In Parkinson's disease, impaired function of mitochondrial complex I is involved in selective degeneration of dopamine neurons in the substantia nigra. Mitochondria are now considered to play an active role in neuronal death process through activating "intrinsic" apoptotic signaling, in addition to production of reactive oxygen species. This paper presents our recent findings on new functions of mitochondria in regulation of their redox state and function through reversible "S-glutathionylation", a mixed disulfide binding between sulfhydryl groups of GSH and protein cysteine in complex I subunits.

Glutathione redox status in mitochondria and cytoplasm differentially and sequentially activates apoptosis cascade in dopamine-melanin-treated SH-SY5Y cells.

Neuromelanin (NM)-containing dopaminergic neurons in the substantia nigra are selectively vulnerable in Parkinson's disease (PD), suggesting the involvement of NM in the pathogenesis. NM is composed of protein, lipid, trace metals and melanin component, a mixture of eumelanin produced from dopamine (DA)-quinone and pheomelanin containing 5-S-cyteinyl-DA-quinone. We reported that NM induces mitochondria-mediated apoptosis in human dopaminergic SH-SY5Y cells, which was suppressed completely by Protease K-treatment, suggesting the essential requirement for the protein component.

[Preventive therapy in middle-aged and elderly persons selected from the population-based screening by mass miniature radiography--methodological aspect and adverse reactions].

The notification rate of tuberculosis in Japan was 31.0 per 100,000 in 2000. The rate was especially high among the elderly population, reaching 85.