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A Fusion of Pathology in Diabetic Neuropathy MEOX2 Linked With

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A Fusion of Pathology in Diabetic Neuropathy MEOX2 Linked With RESEARCH HIGHLIGHTS NEUROLOGICAL DISORDERS A fusion of pathology in diabetic neuropathy The fusion of proinsulin-expressing bone of factors have been implicated in the the researchers showed that the treatment of marrow cells with neurons could be a process. diabetic rats with insulin led to a reduction in key event in the development of diabetic Chan and colleagues had previously the number of proinsulin-positive cells and neuropathy, according to a recent report found proinsulin- and insulin-positive prevented the prolongation of motor nerve by Lawrence Chan and colleagues. cells — which are normally confined conduction velocity — a sign of neuropathy Diabetic peripheral neuropathy is the to the pancreas — in various organs in — confirming that the appearance of these leading cause of non-traumatic limb mouse and rat models of diabetes, and had cells was due to hyperglycaemia. amputations. The symptoms can be shown that most of these extrapancreatic How the mechanism described by Chan widespread, from numbness, pain and insulin-producing cells originated in the and colleagues relates to several other tingling of the extremities to problems bone marrow. In their latest study, the factors that have been implicated in with the digestive tract, bladder infections researchers discovered that in diabetic diabetic neuropathy, including oxidative and impotence. But the chain of events mice and rats with neuropathy, bone- stress and growth factor deficiency, that leads to nerve damage in diabetes is marrow-derived cells that expressed remains an open question. not well described, and current treatments proinsulin fused with neurons in the Rebecca Craven are designed to relieve discomfort and sciatic nerve and dorsal root ganglion, References and links prevent further tissue damage. leading to cellular dysfunction and ORIGINAL RESEARCH PAPER Terashima, T. et al. The The main risk factor for diabetic accelerated apoptosis. fusion of bone-marrow-derived proinsulin-expressing cells neuropathy is hyperglycaemia, and the The hybrid cells expressed proinsulin and with nerve cells underlies diabetic neuropathy. Proc. Natl Acad. Sci. USA 22 August 2005 (doi:10.1073/ progression of neuropathy depends on tumour necrosis factor-α (TNFα), a cytokine pnas.0505717102) the degree of glycaemic control in type 1 that is known to be involved in peripheral FURTHER READING Kojima, H. Extrapancreatic insulin- and type 2 diabetes. How hyperglycaemia neuropathy, and only neurons marked by producing cells in multiple organs in diabetes. Proc. Natl Acad. Sci. USA 101, 2458–2463 (2004) | Yasuda, H. et al. leads to diabetic complications, including proinsulin expression showed abnormal Diabetic neuropathy and nerve regeneration. Prog. neuropathy, is unclear, but a number calcium homeostasis and apoptosis. Crucially, Neurobiol. 69, 229–285 (2003) NEURODEGENERATIVE DISORDERS MEOX2 linked with Alzheimer’s disease Despite many recent advances, the pathogen- The authors compared profiles of mRNA Following on from these findings, Wu and esis of Alzheimer’s disease is still unclear. Wu expression in diseased human brain endothe- colleagues investigated the role of MEOX2 and colleagues bring us another step closer to lial cells with control samples to identify targets in the clearance of the abnormal amyloid-β understanding this process by describing how in Alzheimer’s disease. This revealed that the protein. Mice with only one copy of Meox2 the gene MEOX2 (mesenchyme homeobox 2, expression of a small subset of genes, which showed decreased expression of lipoprotein also known as GAX) contributes to neuronal includes the homeobox gene MEOX2, is receptor-related protein 1 (LRP), which is and vascular dysfunction in this disorder. altered in the disease — specifically, MEOX2 a clearance receptor that is involved in the is expressed at a lower level in cells affected efflux of amyloid-β. However, the reduction by Alzheimer’s disease than in healthy cells. in LRP expression was reversed on transduc- Because homeobox genes have key roles in tion of Meox2 into diseased brain endothelial vascular differentiation, the authors speculated cells. that restoring GAX expression could correct At present, there is no cure for Alzheimer’s the abnormalities in the neurovasculature in disease. The establishment of a link between Alzheimer’s disease. the decreased expression of MEOX2 and the By first silencing and then restoring MEOX2 impaired neurovascular functions that are expression, the authors showed that MEOX2 thought to be involved in the pathology of plays an important part in two important proc- this debilitating disease make this homeobox esses. As well as stimulating the formation of gene an attractive target for the treatment of new blood vessels (angiogenesis), a process that Alzheimer’s disease. is impaired in Alzheimer’s disease, rest oration Samantha Barton of GAX expression also increased the suppres- References and links sion of a transcription factor — the AFX-1 ORIGINAL RESEARCH PAPER Wu, Z. et al. Role of the MEOX2 homeobox gene in neurovascular dysfunction in forkhead transcription factor — that is involved Alzheimer disease. Nature Med. 14 August 2005 (doi:10.1038/ in apoptosis. nm1287) Image courtesy of D. Jones. 752 | OCTOBER 2005 | VOLUME 6 www.nature.com/reviews/neuro © 2005 Nature Publishing Group .
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