New Functions of APC/C Ubiquitin Ligase in the Nervous System and Its Role in Alzheimer's Disease

International Journal of Molecular Sciences
Tanja FuchsbergerJose Vina

Abstract

The E3 ubiquitin ligase Anaphase Promoting Complex/Cyclosome (APC/C) regulates important processes in cells, such as the cell cycle, by targeting a set of substrates for degradation. In the last decade, APC/C has been related to several major functions in the nervous system, including axon guidance, synaptic plasticity, neurogenesis, and neuronal survival. Interestingly, some of the identified APC/C substrates have been related to neurodegenerative diseases. There is an accumulation of some degradation targets of APC/C in Alzheimer's disease (AD) brains, which suggests a dysregulation of the protein complex in the disorder. Moreover, recently evidence has been provided for an inactivation of APC/C in AD. It has been shown that oligomers of the AD-related peptide, Aβ, induce degradation of the APC/C activator subunit cdh1, in vitro in neurons in culture and in vivo in the mouse hippocampus. Furthermore, in the AD mouse model APP/PS1, lower cdh1 levels were observed in pyramidal neurons in CA1 when compared to age-matched wildtype mice. In this review, we provide a complete list of APC/C substrates that are involved in the nervous system and we discuss their functions. We also summarize recent studies that show neurobiological ef...Continue Reading

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Citations

Nov 15, 2017·Cold Spring Harbor Symposia on Quantitative Biology·Pablo Lara-GonzalezArshad Desai
Feb 28, 2019·The Cerebellum·Jerry Vriend, Robert B Tate
Oct 25, 2017·The Journal of Experimental Medicine·Axel MontagneBerislav V Zlokovic
Feb 9, 2021·Mechanisms of Ageing and Development·Hang LiuYing Ma
Aug 28, 2021·Genes·Kyle R CochranSupriyo De

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Methods Mentioned

BETA
ubiquitination
GTPase
gene-trap
transgenic

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