Review articleApoptosis versus axon pruning: Molecular intersection of two distinct pathways for axon degeneration
Section snippets
Introduction to neuronal apoptosis and axon pruning
Neuronal apoptosis occurs extensively and plays a critical role during the development of the nervous system (Burek and Oppenheim, 1996). During nervous system development neurons are produced in excess to ensure productive connections are made to the appropriate targets. Neurons that are unable to successfully innervate their targets, or are no longer necessary, are selectively eliminated by the activation of the apoptotic pathway. This selective elimination of non-productive neurons ensures
Compartmentalized chambers to investigate the molecular pathways of apoptosis versus axon pruning
The model system most frequently used to study the molecular pathways of neuronal apoptosis and axon pruning are developing peripheral neurons (e.g. sympathetic neurons, Dorsal Root Ganglion neurons) in the context of NGF deprivation (Geden and Deshmukh, 2016; Kristiansen and Ham, 2014). Neurons globally deprived of NGF (from both soma and axons) activate the apoptotic pathway which results in the death and degeneration of the entire cell, both soma and axons. Indeed, NGF deprivation of
Molecular pathway of neuronal apoptosis
The key mediators of apoptosis are caspases, a family of cysteine proteases that cleave specific cellular substrates to cause rapid cell death (Denault and Salvesen, 2002)(Fig. 2). In sympathetic neurons undergoing apoptosis due to NGF deprivation, the mechanism by which caspases are activated has been well-studied and is known to occur via the mitochondrial (intrinsic) pathway (Fricker et al., 2018; Kristiansen and Ham, 2014). NGF deprivation results in decreased signaling from the survival
Molecular pathway of axon pruning
The apoptosis and axon pruning pathways share many of the same proteins but with key differences that are highlighted here (Fig. 2). It is crucial to note here that while both apoptosis and axon pruning can be triggered in peripheral neurons with NGF deprivation, the context of NGF deprivation is essential to consider as it results in the engagement of distinct pathways. Whereas apoptosis is engaged in the context of global deprivation of entire neuron (both soma and axons), axon pruning is
Acknowledgement
This work was supported by grant from National Institutes of Health (GM118331) to MD.
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