INVESTIGADORES
PODEROSO Juan Jose
congresos y reuniones científicas
Título:
Mitochondrial nitric oxide, aging and neurodegeneration
Autor/es:
PODEROSO JJ
Lugar:
Aguas de Lindoia, Brasil
Reunión:
Congreso; IV Meeting of the South American Group of the Society for Free Radical Biology and Medicine.; 2005
Institución organizadora:
South American Group of the Society for Free Radical Biology and Medicine.
Resumen:
In the brain, physiological or pathological processes like ageing and neurodegeneration determine loss of intellectual, behavioral and fine motor responses. They all have in common the presence of oxidative or nitrative stress in neurons and glia, dysfunctional mitochondria and the accumulation of abnormal proteins, i.e. amyloid substance in Alzheimer’s disease or Lewy bodies in Parkinson disease (PD). To reconcile the mechanisms, we regard to the biochemistry of nitric oxide (NO) in the CNS. NO increases the mitochondrial production of oxygen species leading to oxidative stress and proapoptotic signaling pattern; oxidative and nitrative stress are contributed by direct reactions between NO and dopamine, the synaptic mediator of nigrostriatal connections. NO excess conducts to complex I nitration or nitrosylation and dysfunction, a hallmark of PD. Many years ago, we proposed increase of NOS1 expression in PD that agrees with the finding of 3-nytrotyrosine in Lewy bodies or, after experimental administration of MPTP. Moreover, the modulation of brain or mitocondrial nitric oxide synthase (mtNOS) was observed by us in early rat development. Changes in the redox status are associated to variations in ERK traffic to mitochondria and nucleus, modifying the protective effects of this MAPK. Accordingly, we recently detected mtNOS and H2O2 increase in rat ageing, a condition with progressive ERK decrease. Effects of nitration and impairment of ubiquinitation and oxidative damage to mtDNA should restrict mitochondrial protein turnover, thus favoring the accumulation of abnormal proteins. It is surmised that increased NO utilization in mitochondria due to different causes and in selected brain areas is the initial event for ageing decay  or neurodegeneration.