The production and accumulation of the beta amyloid protein (Abeta) is a key event in the cascade of oxidative and inflammatory processes that characterizes Alzheimer's disease (AD). A multi-subunit enzyme complex, referred to as gamma (gamma) secretase, plays a pivotal role in the generation of Abeta from its parent molecule, the amyloid precursor protein (APP). Four core components (presenilin, nicastrin, aph-1, and pen-2) interact in a high-molecular-weight complex to perform intramembrane proteolysis on a number of membrane-bound proteins, including APP and Notch. Inhibitors and modulators of this enzyme have been assessed for their therapeutic benefit in AD. However, although these agents reduce Abeta levels, the majority have been shown to have severe side effects in pre-clinical animal studies, most likely due to the enzymes role in processing other proteins involved in normal cellular function. Current research is directed at understanding this enzyme and, in particular, at elucidating the roles that each of the core proteins plays in its function. In addition, a number of interacting proteins that are not components of gamma-secretase also appear to play important roles in modulating enzyme activity. This review will discuss the structural and functional complexity of the gamma-secretase enzyme and the effects of inhibiting its activity.

The prevalence of ID at 4 and 5 mo of age in predominantly breastfed, term infants was 21.4% and 36.4%, respectively. The study generates evidence for considering iron supplementation for well-babies from 4 mo of age, instead of the currently recommended 6 mo by National Iron plus Initiative in India.

CD147, also known as basigin, EMMPRIN, neurothelin, TCSF, M6, HT7, OX47, or gp42, is a transmembrane glycoprotein of the immunoglobulin super-family. It is expressed in many neuronal and non-neuronal tissues including the hippocampus, pre-frontal cortex thyroid, heart, early erythroid, amygdala, and placenta. This protein is involved in various cellular and biological functions, such as lymphocyte migration and maturation, tissue repair cancer progression, T and B lymphocyte activation, and induction of extracellular matrix metalloproteinase. The CD147 protein interacts with other proteins such as cyclophilin A (CyPA), Cyclophilin B (CyPB), sterol carrier protein (SCP), caveolin-1 and integrins, and can influence amyloid-β (Aβ) peptide levels, a protein that is central to Alzheimer's disease (AD) pathogenesis. Mechanisms by which CD147 regulate Aβ levels remain unclear, thus in this review we discuss its involvement in Aβ production and clearance and potential mechanisms by which controlling CD147 levels could impact on Aβ accumulation and AD pathogenesis.

Baculoviral protein expression in insect cells has been previously used to generate large quantities of a protein of interest for subsequent use in biochemical and structural analyses. The MultiBac baculovirus protein expression system has enabled, the use of a single baculovirus to reconstitute a protein complex of interest, resulting in a larger protein yield. Using this system, we aimed to reconstruct the gamma (γ)-secretase complex, a multiprotein enzyme complex essential for the production of amyloid-β (Aβ) protein. A MultiBac vector containing all components of the γ-secretase complex was generated and expression was observed for all components. The complex was active in processing APP and Notch derived γ-secretase substrates and proteolysis could be inhibited with γ-secretase inhibitors, confirming specificity of the recombinant γ-secretase enzyme. Finally, affinity purification was used to purify an active recombinant γ-secretase complex. In this study we demonstrated that the MultiBac protein expression system can be used to generate an active γ-secretase complex and provides a new tool to study γ-secretase enzyme and its variants.

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