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To Survive or to Die: How Neurons Deal with it

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Acute Neuronal Injury

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Abstract

Unlike the majority of cells in the organism, neurons have only two options during their entire existence, to survive or to die. As a result, they have evolved elaborate mechanisms to determine which path they will follow in response to a multitude of internal and external signals, and to the wear-and-tear associated with the aging process. Until recently, activation of the calcium-dependent protease, calpain, had been traditionally associated with neurodegeneration. This chapter will review recent findings that indicate that two of the major calpain isoforms present in the brain, calpain-1 and calpain-2, play opposite functions in neuronal survival/death. Thus, calpain-1 activation, downstream of synaptic NMDA receptors, is part of a neuronal survival pathway through the truncation of PHLPP1 and the stimulation of the Akt pathway. In contrast, calpain-2 activation is downstream of extrasynaptic NMDA receptors and is neurodegenerative through the truncation of the phosphatase, STEP, and the activation of the p38 protein kinase. These findings have major significance for our understanding of neurological conditions associated with neurodegeneration and for the development of new therapeutic approaches to prevent neuronal death in these disorders.

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Acknowledgements

This work was supported by grant P01NS045260-01 from NINDS (PI: Dr. C.M. Gall), grant R01NS057128 from NINDS to M.B., and grant R15MH101703 from NIMH to X.B. X.B. is also supported by funds from the Daljit and Elaine Sarkaria Chair.

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  1. Graduate College of Biomedical Sciences, Western University of Health Sciences, Pomona, CA, USA

    Yubin Wang & Michel Baudry

  2. College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, USA

    Xiaoning Bi

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Correspondence to Michel Baudry .

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  1. Department of Neurology, VA Greater Los Angeles Healthcare System, North Hills, California, USA

    Denson G. Fujikawa

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Wang, Y., Bi, X., Baudry, M. (2018). To Survive or to Die: How Neurons Deal with it. In: Fujikawa, D. (eds) Acute Neuronal Injury. Springer, Cham. https://doi.org/10.1007/978-3-319-77495-4_2

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