Syed Z. Imam

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Mutations in parkin, an E3 ubiquitin ligase, are the most common cause of autosomal-recessive Parkinson's disease (PD). Here, we show that the stress-signaling non-receptor tyrosine kinase c-Abl links parkin to sporadic forms of PD via tyrosine phosphorylation. Under oxidative and dopaminergic stress, c-Abl was activated in cultured neuronal cells and in(More)
Methamphetamine (METH)-induced dopaminergic neurotoxicity is believed to be produced by oxidative stress and free radical generation. The present study was undertaken to investigate if METH generates peroxynitrite and produces dopaminergic neurotoxicity. We also investigated if this generation of peroxynitrite can be blocked by a selective peroxynitrite(More)
The ends of linear chromosomes are capped and protected by protein-DNA complexes termed telomeres. Consequences of telomere dysfunction include genomic instability that can contribute to neoplastic transformation and progression. Telomere binding proteins interact with numerous proteins involved in DNA repair, underscoring the importance of regulating DNA(More)
Cocaine is a widely used drug of abuse and psychostimulant that acts on the central nervous system by blocking the dopamine reuptake sites. PC12 cells, a rat pheochromocytoma clonal line, in the presence of nerve growth factor (NGF), multiply and differentiate into competent neurons that can synthesize, store, and secrete the neurotransmitter dopamine (DA).(More)
NO reacts spontaneously with superoxide to produce the potent oxidant peroxynitrite. Studies were designed to examine the role of NO-derived oxidants and peroxynitrite on the regulation of Na(+),K(+)-ATPase activity by angiotensin II (ANG II) freshly isolated rat proximal tubules. At picomolar concentrations ANG II stimulates Na(+),K(+)-ATPase activity, but(More)
Knocking out of Nurr1 gene, a member of nuclear receptor superfamily, causes selective agenesis of dopaminergic neurons in midbrain. Reduced expression of Nurr1 increases the vulnerability of mesencephalic dopamine neurons to dopaminergic toxins. We evaluated the role of nitric oxide as a possible mechanism for this increased susceptibility. Increased(More)
Aging is associated with increased susceptibility to neuronal loss and disruption of cerebral function either as a component of senescence, or as a consequence of neurodegenerative disease or stroke. Here we report differential changes in the repair of oxidative DNA damage in various brain regions during aging. We evaluated mitochondrial and nuclear(More)
Some of the damage to the CNS that is observed following amphetamine and methamphetamine (METH) administration is known to be linked to increased formation of free radicals. This increase could be, in part, related to mitochondrial dysfunction and/or cause damage to the mitochondria, thereby leading to a failure of cellular energy metabolism and an increase(More)
Methamphetamine (METH) produces dopaminergic neurotoxicity by the production of reactive oxygen (ROS) and nitrogen (RNS) species. The role of free radicals has also been implicated in the process of aging. The present study was designed to evaluate whether METH-induced dopaminergic neurotoxicity and hyperthermia is a result of peroxynitrite production and(More)
The proliferation and migration of arterial smooth muscle cells (SMCs) are key events in the vascular restenosis that frequently follows angioplasty. Furthermore, SMC migration and neointimal hyperplasia are promoted by degradation of the extracellular matrix by matrix metalloproteinases (MMPs). Because we demonstrated previously that the proinflammatory(More)