A H Schapira

..Drugs, toxins and deficiency of nuclear encoded proteins that are targeted at mitochondria are now recognized as important causes of secondary mitochondrial respiratory chain deficiency...

..In any event, mitochondria present an important target for future strategies for 'neuroprotection' to prevent or retard neurodegeneration...

..The actions of specific toxins, e.g., MPTP continue to play an important role in our understanding of pathogenesis of neurodegeneration, particularly in PD...

..002) in those with this mutation who smoked. This reflects an increase in mitochondrial mass with the 11,778 mutation. This effect was not observed with the 3460 mutation even though the complex deficiency was much more severe...

..Clarifying the role of mitochondria in pathogenesis may provide opportunities for the development of treatments designed to reverse or prevent neurodegeneration...

..These results suggest that the nuclear environment can influence the expression of the biochemical defect in LHON patients with the A3460G mutation...

..A potential role for inborn mitochondrial defects in these disorders has not yet been defined but is currently attracting interest...

..These findings have important implications for our understanding of complex I dysfunction in the pathogenesis of 3460 Leber's hereditary optic neuropathy...

..A significant proportion of LHON patients had circulating antibodies to tubulin protein. This finding supports the theory that autoimmunity may play some role in the pathogenesis of LHON...

..Furthermore, affected relative pairs did not share HLA genotypes more than discordant pairs. We conclude that the HLA-DR locus is not a major genetic determinant for the development of blindness in LHON...

..Transfer of patient mitochondria with residual mtDNA levels to control cells devoid of mtDNA (rho0 cells) led to restoration of mtDNA levels and, hence, suggests a nuclear involvement in the depletion...

..However, the clinical and experimental data reviewed suggest differences in the phenotype associated with each of the three mutations which may reflect variation in the disease mechanisms resulting in this common end-point...

..There was no association between LHON and any genotype. We conclude that the classical class I MHC loci are not major determinants of the development of blindness in LHON...

..Thus, NO(*-) may 'prime' the respiratory chain to the effects of MPP(+). These data provide evidence for an interaction between NO(*-) and MPP(+) at the level of the respiratory chain...

..mitochondrial complex I activity is significantly reduced in IPD, intrinsically low expression of glycolytic enzymes, together with disease-related reduction in complex I activity, may be a contributory factor predisposing nigral neurons..

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..This suggests other antioxidants, such as ubiquinol and GSH, may be more important in protecting liver mitochondria and MRC from lipid peroxidation...

..It is concluded that the primary mtDNA mutations currently associated with LHON are not responsible for the prominence of optic nerve disease in Devic's neuromyelitis optica...

..The value of existing and novel continuous drug delivery systems in PD is seen as providing simplified regimens, maintenance of motor control, reduction in motor complications and improved patient adherence to drug use...

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..Future research directed toward developing neuroprotective strategies may reduce oxidative stress and stabilize or improve mitochondrial function...