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Aberrant Expression of RCAN1 in Alzheimer’s Pathogenesis: A New Molecular Mechanism and a Novel Drug Target

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Abstract

AD, a devastating neurodegenerative disorder, is the most common cause of dementia in the elderly. Patients with AD are characterized by three hallmarks of neuropathology including neuritic plaque deposition, neurofibrillary tangle formation, and neuronal loss. Growing evidences indicate that dysregulation of regulator of calcineurin 1 (RCAN1) plays an important role in the pathogenesis of AD. Aberrant RCAN1 expression facilitates neuronal apoptosis and Tau hyperphosphorylation, leading to neuronal loss and neurofibrillary tangle formation. This review aims to describe the recent advances of the regulation of RCAN1 expression and its physiological functions. Moreover, the AD risk factors-induced RCAN1 dysregulation and its role in promoting neuronal loss, synaptic impairments and neurofibrillary tangle formation are summarized. Furthermore, we provide an outlook into the effects of RCAN1 dysregulation on APP processing, Aβ generation and neuritic plaque formation, and the possible underlying mechanisms, as well as the potential of targeting RCAN1 as a new therapeutic approach.

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Abbreviations

AD:

Alzheimer’s disease

RCAN1:

Regulator of calcineurin 1

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Acknowledgments

This work was supported by Canadian Institutes of Health Research (CIHR) Operating Grant TAD-117948. W.S. is the holder of the Tier 1 Canada Research Chair in Alzheimer's Disease.

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  1. Townsend Family Laboratories, Department of Psychiatry, Brain Research Center, Graduate Program in Neuroscience, The University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC, Canada, V6T 1Z3

    Yili Wu, Philip T. T. Ly & Weihong Song

  2. Ministry of Education Key Laboratory of Child Development and Disorders, and Chongqing City Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders, Children’s Hospital of Chongqing Medical University, 136 Zhongshan Er Lu, Chongqing, 400014, China

    Yili Wu & Weihong Song

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Wu, Y., Ly, P.T.T. & Song, W. Aberrant Expression of RCAN1 in Alzheimer’s Pathogenesis: A New Molecular Mechanism and a Novel Drug Target. Mol Neurobiol 50, 1085–1097 (2014). https://doi.org/10.1007/s12035-014-8704-y

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