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Leucine, nutrient signal and substrate for the branched chain aminotransferase (BCAT) activates the mechanistic target of rapamycin (mTORC1) and regulates autophagic flux, mechanisms implicated in the pathogenesis of neurodegenerative conditions such as Alzheimer's disease (AD). BCAT is upregulated in AD, where a moonlighting role, imparted through its redox-active CXXC motif, has been suggested. Here we demonstrate that the redox state of BCAT signals differential phosphorylation by protein kinase C (PKC) regulating the trafficking of cellular pools of BCAT. We show inter-dependence of BCAT expression and proteins associated with the P13K/Akt/mTORC1 and autophagy signalling pathways. In response to insulin or an increase in ROS, BCATc is trafficked to the membrane and docks via palmitoylation, which is associated with BCATc-induced autophagy through PKC phosphorylation. In response to increased levels of BCATc, as observed in AD, amyloid β (Aβ) levels accumulate due to a shift in autophagic flux. This effect was diminished when incubated with leucine, indicating that dietary levels of amino acids show promise in regulating Aβ load. Together these findings show that increased BCATc expression, reported in human AD brain, will affect autophagy and Aβ load through the interdependence of its redox-regulated phosphorylation offering a novel target to address AD pathology., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Ageing leads to a number of changes in the body including the macula. Detailed imaging using optical coherence tomography have enabled in vivo studies of how macula changes with age. Here we systematically review 49 studies (9115 participants and 11,577 eyes) to provide an overview of how ageing manifests in the macula of the elderly focusing on clinical relevant measures that are thicknesses and volumes of different macular areas. Ageing seems to increase center point foveal thickness. Ageing does not seem to change the center subfield thickness significantly. Ageing decreases the inner and outer macular thickness, and the overall macular thickness and volume. Studies find that specific retinal layers at specific locations seem to be the contributor to these changes. These findings confirm that age-related changes suggested in histological studies are measurable in vivo on thickness and volume and differ depending on location. Studies are needed to explore reasons for the large variance in measurements and how ageing by itself contributes to development of macular disease., (Copyright © 2016 Elsevier B.V. All rights reserved.)