Recent visual laterality studies have included trials in which critical stimulus information is presented simultaneously in both visual half-fields and, thereby, simultaneously to both cerebral hemispheres. To investigate interhemispheric interaction, researchers compare performance on bilateral redundant trials with performance on unilateral trials in which a single copy of the target is presented to one hemisphere or the other. The authors used the identification of nonword letter trigrams to examine the relationship between unilateral and bilateral performance when the 2 types of trials were equated for the number of locations stimulated (Experiment 1) and the number of redundant copies of the target (Experiment 2). Results suggest that when the number of stimulated locations is held constant, each of 2 copies of a target stimulus can be processed with the same efficiency and the same strategy as it would have been had it been the only copy.

Caspase-3 activity increased dramatically in cytosolic extracts of rat cerebellar granule cells exposed to apoptotic conditions (basal medium Eagle (BME) containing 5 mM K+ without serum) when assayed with Ac-DEVD-amc, but not with Ac-YVAD-afc, a preferred substrate for caspase-1. This provided a basis to examine relationships between enzyme activity and cell viability for purposes of selecting an optimal time for comparing neuroprotective agents or strategies. Exposure of neurons to an apoptotic medium containing 5 mM K+ in absence of serum led to a rapid 5- to 10-fold increase in caspase-3 within 2-4 hr but without significant cell loss, or morphological alterations. Exposure to apoptotic medium followed by replacement with maintenance medium containing 25 mM K+ and serum led to a rapid fall in caspase-3 and prevention of cell death. This strategy was not effective after 13 hr exposure despite a large fall in enzyme activity. These temporal changes infer systems for rapid enzyme turnover and/or activation of cytoplasmic components linked to later DNA degradation. The effects of cycloheximide point to requirements for protein synthesis, and those of Glu exclude a caspase-3 dependent pathway for necrotic cell damage. Brief treatment with 10 microM LIGA20, an anti-necrotic agent, also attenuated cell loss and caspase-3 activity, indicating a broad spectrum of neuroprotection. Rapid and long-lasting effects, together with its biophysical properties, suggest that this semisynthetic ganglioside acted upstream at or near a membrane site. As such, gangliosides provide useful agents to further probe pathways relevant to neuronal death in culture.

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Secretases are named for enzymes processing amyloid precursor protein (APP), a prototypic type-1 membrane protein. This led directly to discovery of novel Aspartyl proteases (beta-secretases or BACE), a tetramer complex gamma-secretase (gamma-SC) containing presenilins, nicastrin, aph-1 and pen-2, and a new role for metalloprotease(s) of the ADAM family as a alpha-secretases. Recent advances in defining pathways that mediate endosomal-lysosomal-autophagic-exosomal trafficking now provide targets for new drugs to attenuate abnormal production of fibril forming products characteristic of AD. A key to success includes not only characterization of relevant secretases but mechanisms for sorting and transport of key metabolites to abnormal vesicles or sites for assembly of fibrils. New developments we highlight include an important role for an 'early recycling endosome' coated in retromer complex containing lipoprotein receptor LRP-II (SorLA) for switching APP to a non-amyloidogenic pathway for alpha-secretases processing, or to shuttle APP to a 'late endosome compartment' to form Abeta or AICD. LRP11 (SorLA) is of particular importance since it decreases in sporadic AD whose etiology otherwise is unknown.