Nerve growth factor (NGF) promotes neuronal survival and differentiation and stimulates neurite outgrowth. NGF is synthesized as a precursor, proNGF, which undergoes posttranslational processing to generate mature b-NGF. It has been assumed that, in vivo, NGF is largely processed into the mature form and that mature NGF accounts for the biological activity. However, we recently showed that proNGF is abundant in CNS tissues whereas mature NGF is undetectable, suggesting that proNGF has biological functions beyond its role as a precursor. To determine whether proNGF exhibits biological activity, we mutagenized the precursor-processing site and expressed unprocessed, cleavage-resistant proNGF protein in insect cells. Survival and neurite outgrowth assays on murine superior cervical ganglion neurons and PC12 cells indicated that proNGF exhibits neurotrophic activity similar to mature 2.5S NGF, but is approximately fivefold less active. ProNGF binds to the high-affinity receptor, TrkA, as determined by cross-linking to PC12 cells, and is also slightly less active than mature NGF in promoting phosphorylation of TrkA and its downstream signaling effectors, Erk1/2, in PC12 and NIH3T3-TrkA cells. These data, coupled with our previous report that proNGF is the major form of NGF in the CNS, suggest that proNGF could be responsible for much of the biological activity normally attributed to mature NGF in vivo.
Alpinia calcarata Rosc. of Zingiberaceae popularly known also as Lesser galangal has a widespread occurrence in India, Malaysia, Bangladesh and China. Drugs prepared by using rhizomes of Alpinia calcarata are used in the treatment of rheumatism, bronchial catarrah and asthma. They are also used against infection of the skin and also possess antibacterial activity. LCMS/MS study has provided chemical profile present in the methanolic rhizome extract. LCMS/MS full scan was performed on ESI ionization mode using both polarities. Among the 37 compounds identified Catechol, Citral, Protocatechuic acid, Nerol, Umbelliferone, Chrysin, Vanillic acid, Nerolidol have more prominent activities in different levels. The high selectivity of MS-MS detection allowed the development of a very specific and rapid method for the determination of components in methanolic rhizome extracts of Alpinia calcarata.
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