Review Article Nuclear transport, oxidative stress, and neurodegeneration
Vivek P. Patel, Charleen T. Chu
Center for Neuroscience at the University of Pittsburgh1; Department of Pathology, Division of Neuropathology2, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA
Received February 22, 2011; accepted February 27, 2011; Epub February 28, 2011; published March 31, 2011
Abstract: Trafficking of transcription factors between the cytoplasm and the nucleus is an essential aspect of signal transduction, which is particularly challenging in neurons due to their highly polarized structure. Disruption in the subcellular localization of many proteins, including transcription factors, is observed in affected neurons of human neurodegenerative diseases. In these diseases, there is also growing evidence supporting alterations in nuclear transport as potential mechanisms underlying the observed mislocalization of proteins. Oxidative stress, which plays a key pathogenic role in these diseases, has also been associated with significant alterations in nuclear transport. After providing an overview of the major nuclear import and export pathways and discussing the impact of oxidative injury on nuclear trafficking of proteins, this review synthesizes emerging evidence for altered nuclear transport as a possible mechanism in the pathogenesis of neurodegenerative diseases. Potential strategies to overcome such deficits are also discussed. (IJCEP1102006).
Address all correspondence to: Charleen T. Chu, MD, PhD Department of Pathology, Division of Neuropathology University of Pittsburgh School of Medicine Room W958 BST 200 Lothrop Street Pittsburgh, PA 15213, USA. Tel: (412) 383-5379 Fax: (412) 648-9172 E-mail: email@example.com