Nat Neurosci. 2007 Nov;10(11):1361-8.
Scholz J, Woolf CJ.
Neural Plasticity Research Group, Department of Anesthesia and Critical Care, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Nociceptive pain results from the detection of intense or noxious stimuli by specialized high-threshold sensory neurons (nociceptors), a transfer of action potentials to the spinal cord, and onward transmission of the warning signal to the brain. In contrast, clinical pain such as pain after nerve injury (neuropathic pain) is characterized by pain in the absence of a stimulus and reduced nociceptive thresholds so that normally innocuous stimuli produce pain. The development of neuropathic pain involves not only neuronal pathways, but also Schwann cells, satellite cells in the dorsal root ganglia, components of the peripheral immune system, spinal microglia and astrocytes. As we increasingly appreciate that neuropathic pain has many features of a neuroimmune disorder, immunosuppression and blockade of the reciprocal signaling pathways between neuronal and non-neuronal cells offer new opportunities for disease modification and more successful management of pain.

Glia. 2008 Feb;56(3):306-17.
Developmental loss of NT-3 in vivo results in reduced levels of myelin-specific proteins, a reduced extent of myelination and increased apoptosis of Schwann cells.
Woolley AG, Tait KJ, Hurren BJ, Fisher L, Sheard PW, Duxson MJ.
Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
This work investigates the role of NT-3 in peripheral myelination. Recent articles, based in vitro, propose that NT-3 acting through its high-affinity receptor TrkC may act to inhibit myelin formation by enhancing Schwann cell motility and/or migration. Here, we investigate this hypothesis in vivo by examining myelination formation in NT-3 mutant mice. On the day of birth, soon after the onset of myelination, axons showed normal ensheathment by Schwann cells, no change in the proportion of axons which had begun to myelinate, and no change in either myelin thickness or number of myelin lamellae. However in postnatal day 21 mice, when myelination is substantially complete, we observed an unexpected reduction in mRNA and protein levels for MAG and P(0), and in myelin thickness. This is the opposite result to that predicted from previous in vitro studies, where removal of an inhibitory NT-3 signal would have been expected to enhance myelination. These results suggest that, in vivo, the importance of NT-3 as a major support factor for Schwann cells (Meier et al., (1999) J Neurosci 19:3847-3859) over-rides its potential role as an myelin inhibitor, with the net effect that loss of NT-3 results in degradation of Schwann cell functions, including myelination. In support of this idea, Schwann cells of NT-3 null mutants showed increased expression of activated caspase-3. Finally, we observed significant reduction in width of the Schwann cell periaxonal collar in NT-3 mutant animals suggesting that loss of NT-3 and resulting reduction in MAG levels may alter signaling at the axon-glial interface.

The New York Times recently digitized its pre-Internet archives and opened them to the public, so today I ran a search and found a single mention of Dejerine-Sottas disease. It’s an interesting article on the use of x-ray crystallography to shed some light on the proteins created by the P0 mutation, one of the mutations that causes Dejerine-Sottas.

Protein Linked to 3 Nerve Ailments

IN two papers representing the work of 19 researchers, scientists reported last week that they had seen, at a molecular level, the damage to an important protein that is the cause of three genetic nerve disorders. Dr. Thomas Bird, a professor at the University of Washington and chief of neurology at the Veterans Affairs hospital in Seattle, who is not associated with the groups who made the reports, said that the papers are examples of where medicine has arrived: at the molecular detail of human disease.

Read more of Protein Linked to 3 Nerve Ailments

Mol Pharm. 2007 Nov 14
Anand P, Kunnumakkara AB, Newman RA, Aggarwal BB.
Cytokine Research Laboratory and Pharmaceutical Development Center, Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030
Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Phase I clinical trials have shown that curcumin is safe even at high doses (12 g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination.
To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life.
Despite the lower bioavailability, therapeutic efficacy of curcumin against various human diseases, including cancer, cardiovascular diseases, diabetes, arthritis, neurological diseases and Crohn’s disease, has been documented. Enhanced bioavailability of curcumin in the near future is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease.