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Transcriptional Factor NF- κ B as a Target for Therapy in Parkinson's Disease

2011; Hindawi Publishing Corporation; Volume: 2011; Linguagem: Inglês

10.4061/2011/216298

2090-8083

Patrick M. Flood, Qian Li, Lynda J. Peterson, Feng Zhang, Jingshan Shi, Hui‐Ming Gao, Jau‐Shyong Hong,

Immune Response and Inflammation

Parkinson's disease (PD) is a neurodegenerative condition characterized by chronic inflammation. Nuclear factor κ B (NF- κ B) is a family of inducible transcription factors that are expressed in a wide variety of cells and tissues, including microglia, astrocytes, and neurons, and the classical NF- κ B pathway plays a key role in the activation and regulation of inflammatory mediator production during inflammation. Activation of the classical NF- κ B pathway is mediated through the activity of the IKK kinase complex, which consists of a heterotrimer of IKK α , IKK β , and IKK γ subunits. Targeting NF- κ B has been proposed as an approach to the treatment of acute and chronic inflammatory conditions, and the use of inhibitors specific for either IKK β or IKK γ has now been found to inhibit neurodegeneration of TH+ DA-producing neurons in murine and primate models of Parkinson's disease. These studies suggest that targeting the classical pathway of NF- κ B through the inhibition of the IKK complex can serve as a useful therapeutic approach to the treatment of PD.