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Selective damage of mitochondrial complex I within the dopaminergic neurons of the substantia nigra is the central event during Parkinson disease. Peroxynitrite is one of the important free radicals probably mediating complex I damage. Peroxynitrite inhibits brain complex I mainly by 3-nitrotyrosine and nitrosothiol formation, but how these modifications alter the structure-function relation of complex I is unclear. Curcumin pretreatment protects brain mitochondria against peroxynitrite in vitro by direct detoxification and prevention of 3-nitrotyrosine formation and in vivo by elevation of total cellular glutathione levels. These results suggest a potential therapeutic role for curcumin against nitrosative stress in neurological disorders.

Selective damage of mitochondrial complex I within the dopaminergic neurons of the substantia nigra is the central event during Parkinson disease. Peroxynitrite is one of the important free radicals probably mediating complex I damage. Peroxynitrite inhibits brain complex I mainly by 3-nitrotyrosine and nitrosothiol formation, but how these modifications alter the structure-function relation of complex I is unclear. Curcumin pretreatment protects brain mitochondria against peroxynitrite in vitro by direct detoxification and prevention of 3-nitrotyrosine formation and in vivo by elevation of total cellular glutathione levels. These results suggest a potential therapeutic role for curcumin against nitrosative stress in neurological disorders.

J. Neurochem. (2010) 113, 807–818. Abstract Hes‐1 and Hes‐5 are downstream effectors of Notch signaling that are known to be involved in different aspects of neural stem cell proliferation and differentiation. Evidence has emerged that Hes‐1 expression can be regulated by alternate signaling pathways independent of canonical Notch/CBF1 interaction. This context‐dependent differential regulation of Hes‐1 expression in neural progenitor gains a lot of importance as it would help in its exponential expansion without the requirement of interaction from neighboring cells during development. Here, we have clearly demonstrated the existence of a population of neural progenitors with Notch/CBF1‐independent Hes‐1 expression in vitro. Further analysis demonstrated the role of FGF2 in activating Hes‐1 expression through the direct binding of ATF2, a JNK downstream target, on Hes‐1 promoter. This raises the possibility for the existence of two distinct populations of neural progenitors – one maintained by Hes‐1 expression exclusively through Notch‐independent mechanism and the other mediating Hes‐1 expression through both canonical Notch and FGF2‐ATF2 pathway. This alternative pathway will insure a constant expression of Hes‐1 even in the absence of canonical Notch intracellular domain‐mediated signaling, thereby maintaining a pool of proliferating neural progenitors required during development.