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Goiran T, Duplan E, Chami M, Bourgeois A, El Manaa W, Rouland L, Dunys J, Lauritzen I, You H, Stambolic V, Biféri MG, Barkats M, Pimplikar SW, Sergeant N, Colin M, Morais VA, Pardossi-Piquard R, Checler F, Alves da Costa C. β-Amyloid Precursor Protein Intracellular Domain Controls Mitochondrial Function by Modulating Phosphatase and Tensin Homolog-Induced Kinase 1 Transcription in Cells and in Alzheimer Mice Models. Biol Psychiatry. 2017 May 3; PubMed.
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University of Dundee
Goiran et al. is a potentially interesting study that ties together two major neurodegenerative disorder pathways of Alzheimer's and Parkinson's.
Very little is known about the upstream transcriptional regulation of Pink-1, so the finding that AICD can regulate Pink-1 transcription is significant. That said, the exact mechanism of how AICD controls Pink-1 transcription is unknown. Furthermore, the evidence for effects on mitophagy were lacking as the authors did not employ standard assays to measure mitophagy.
From a clinical perspective, it would also be interesting if the authors could show in additional patient-derived cells and tissues from AD patients that Pink-1 levels are elevated. It would also be exciting to know whether this Pink-1 upregulation is primarily driving AD pathogenesis or is secondary—studying the impact of APP processing in a Pink-1 null background would aid this.
Overall, an intriguing study that will require additional experiments to flesh out the mechanism and clinical significance of these pathways coverging.
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