Hook Proteins: Association with Alzheimer Pathology and Regulatory Role of Hook3 in Amyloid Beta Generation |
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| Authors: | Lydia Herrmann Caspar Wiegmann Annika Arsalan-Werner Isabel Hilbrich Carsten J?ger Katharina Flach Anne Suttkus Ingolf Lachmann Thomas Arendt Max Holzer |
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| Institution: | 1. Paul Flechsig Institute of Brain Research, Department of Molecular and Cellular Mechanism of Neurodegeneration, University of Leipzig, Leipzig, Germany.; 2. AJ Roboscreen GmbH, Leipzig, Germany.; National Center for Geriatrics and Gerontology, JAPAN, |
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| Abstract: | Defects in intracellular transport are implicated in the pathogenesis of Alzheimer’s disease (AD). Hook proteins are a family of cytoplasmic linker proteins that participate in endosomal transport. In this study we show that Hook1 and Hook3 are expressed in neurons while Hook2 is predominantly expressed in astrocytes. Furthermore, Hook proteins are associated with pathological hallmarks in AD; Hook1 and Hook3 are localized to tau aggregates and Hook2 to glial components within amyloid plaques. Additionally, the expression of Hook3 is reduced in AD. Modelling of Hook3 deficiency in cultured cells leads to slowing of endosomal transport and increases β-amyloid production. We propose that Hook3 plays a role in pathogenic events exacerbating AD. |
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