An initial effect of nerve growth factor on a responsive nerve cell line is to increase intracellular cyclic AMP, which in turn leads to a mobilisation of calcium ions. These events are correlated with structural changes in the plasma membrane, increased cell-substratum adhesion, and neurite outgrowth.

The structures of five neurotrophic molecules have so far been published. Nerve growth factor, fibroblast growth factor and purpurin, have been identified as nerve-cell survival molecules. More recently, brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor have been cloned and sequenced. As all these proteins stimulate the survival of ciliary or sensory neurons, a new cell survival assay is required if novel neurotrophic molecules are to be discovered. P19 teratoma cells differentiate to nerve-like cells in the presence of 5 x 10(-7) M retinoic acid (RA). But when P19 cells are plated in N2 synthetic medium without being exposed to RA, they die within 48 h. In an attempt to identify a molecule(s) that can substitute for RA in promoting P19 survival, we assayed serum-free growth-conditioned media for their ability to promote P19 survival. One cell line from the rat eye secreted a molecule that promoted the survival of P19 cells and some types of nerve cell. We identified this molecule as activin, better known for its role in hormone secretion.

Embryonic chick neural retina cells release glycoprotein complexes, termed adherons, into their culture medium. When adsorbed onto the surface of petri dishes, neural retina adherons increase the initial rate of neural retina cell adhesion; they also stimulate the rate of cell-cell aggregation. Adheron-stimulated adhesion is tissue specific, and the spontaneous aggregation of neural retina cells is inhibited by monovalent Fab' fragments prepared from an antiserum against neural retina adherons. Therefore cell surface antigenic determinants shared with adherons are involved in normal cell-cell adhesions. The particles from the heterogeneous neural retina population contain many proteins and several glycosaminoglycans. The adherons migrate as a symmetrical 12S peak on sucrose gradients and are predominantly 15-nm spheres when examined by electron microscopy. Finally, the specific activity of neural retina adherons increases from embryonic days 7 through 12 and then declines. These results suggest that glycoprotein particles may be involved in some of the adhesive interactions between neural retina cells and between the cells and their environment.

A secreted form of the amyloid (3 protein precursor was isolated from the growth conditioned medium of the PC12 sympathetic nerve-like cell line. This protein is recognized by an antiserum that detects a protein of 140 kDa and a less abundant species of 115 kDa on NaDodSO4/acrylamide gels. The amyloid precursor proteins contain 0-linked sugars and tyrosine sulfate and bind to the glycosaminoglycan heparin. These results suggest a role for extracellular sulfated glycoproteins in the pathogenesis of Alzheimer disease.In patients with Alzheimer disease, filamentous amyloid structures accumulate in the central nervous system (1 2066The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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