Autophagy in the Degeneration of Optic Nerve and Spinal Cord Axons

In many neurological disorders, axonal degeneration is one of the first pathological signs of the disease. It is also of great relevance for disease progression and the persistence of clinical symptoms due to its irreversibility and the important physiological function of the axon. Therefore it is mandatory to better understand the underlying pathophysiological mechanisms in order to design therapeutic strategies. Axonal degeneration has been studied most extensively in the optic nerve and the spinal cord, due to their exposed anatomic localization and clinical relevance. For both structures of the central nervous system, defined lesion models have been established which allow for specific analyses including immunohistochemistry, electron microscopy, proteomics, and live imaging. These techniques have revealed that a rapid and sustained increase of autophagy markers is a common feature of axonal degeneration in various disease models in optic nerve and spinal cord. However, the function of autophagy seems to differ substantially depending on the time point, the subcellular compartment, and the disease model. This is especially important, as opposing effects have been reported with regards to therapeutic modulations of autophagy. In this chapter, we review the current literature on autophagy in axonal degeneration of optic nerve and spinal cord, and identify common themes and future directions.