The Molecular Interplay between Axon Degeneration and Regeneration

Abstract

Neurons face a series of morphological and molecular changes following trauma and in the progression of neurodegenerative disease. In neurons capable of mounting a spontaneous regenerative response, including invertebrate neurons and mammalian neurons of the peripheral nervous system (PNS), axons regenerate from the proximal side of the injury and degenerate on the distal side. Studies of Wallerian degeneration slow (Wld /Ola) mice have revealed that a level of coordination between the processes of axon regeneration and degeneration occurs during successful repair. Here, we explore how shared cellular and molecular pathways that regulate both axon regeneration and degeneration coordinate the two distinct outcomes in the proximal and distal axon segments. © 2018 Wiley Periodicals, Inc. Develop Neurobiol 00: 000-000, 2018.

Intrinsic Determinants of Axon Regeneration

“…Axon growth requires energy, and is therefore influenced by the presence of mitochondria. This issue is discussed in the paper in this issue from (Girouard et al, ). The density of mitochondria in axons has been increased through expression of miro and Armcx1 (Cartoni et al, ; Han et al, ), leading to enhanced regeneration, while lack of mitochondria will trigger axon degeneration.…”

“…These various molecules get to their correct place in the axon via transport and trafficking. The study of these processes is therefore a key area of regeneration research, and is addressed in four papers in this special issue (Girouard et al, ; Murillo and Sousa, ; Petrova and Eva, ; Shah and Goldberg, ).…”

“…These processes are highly controlled by various structural and signaling pathways. Four papers in this issue address this topic (Girouard et al, ; Murillo and Sousa, ; Petrova and Eva, ; Shah and Goldberg, ). CNS neurons are highly polarized and transport is divided into two main fields, somatodendritic and axonal (Bentley and Banker, ; Maeder et al, ).…”

“…These are triggered by adhesion molecules, growth factor receptors, guidance molecules, mechanotransduction. Please see the papers in this issue by (Girouard et al, ; Murillo and Sousa, ). Many of the general signaling pathways are involved, including the AKT and JAK/STAT pathways, control via Rho and Rac, and control via calcium.…”

“…The cytoskeleton is the motor and the structural support of growing axons and also the pathway for axonal transport. The role of the cytoskeleton in regeneration is discussed in the papers in this issue by (Girouard et al, ; Murillo and Sousa, ). The controls for cytoskeletal dynamics are largely understood, and most of the molecules involved in these processes appear to be present in axons at all stages.…”