Free Radic Biol Med. 2007 Dec 4 [Epub ahead of print]

Curcumin treatment alleviates the effects of glutathione depletion in
vitro and in vivo: Therapeutic implications for Parkinson's disease
explained via in silico studies.


Jagatha B, Mythri RB, Vali S, Bharath MM.


Department of Neurochemistry, National Institute of Mental Health and
Neurosciences, 2900, Hosur Road Bangalore 560029, Karnataka, India.


Oxidative stress has been implicated in the degeneration of
dopaminergic neurons in the substantia nigra (SN) of Parkinson's
disease (PD) patients. An important biochemical feature of
presymptomatic PD is a significant depletion of the thiol antioxidant
glutathione (GSH) in these neurons resulting in oxidative stress,
mitochondrial dysfunction, and ultimately cell death. We have earlier
demonstrated that curcumin, a natural polyphenol obtained from
turmeric, protects against peroxynitrite-mediated mitochondrial
dysfunction both in vitro and in vivo. Here we report that treatment
of dopaminergic neuronal cells and mice with curcumin restores
depletion of GSH levels, protects against protein oxidation, and
preserves mitochondrial complex I activity which normally is impaired
due to GSH loss. Using systems biology and dynamic modeling we have
explained the mechanism of curcumin action in a model of mitochondrial
dysfunction linked to GSH metabolism that corroborates the major
findings of our experimental work. These data suggest that curcumin
has potential therapeutic values for neurodegenerative diseases
involving GSH depletion-mediated oxidative stress.


PMID: 18166164 [PubMed - as supplied by publisher]