Autophagy in white matter disorders of the CNS: mechanisms and therapeutic opportunities.

Autophagy is a constitutive process that degrades, recycles and clears damaged proteins or organelles, yet, despite activation of this pathway, abnormal proteins accumulate in neurons in neurodegenerative diseases and in oligodendrocytes in white matter disorders. Here, we discuss the role of autophagy in white matter disorders, including neurotropic infections, inflammatory diseases such as multiple sclerosis, and in hereditary metabolic disorders and acquired toxic-metabolic disorders. Once triggered due to cell stress, autophagy can enhance cell survival or cell death that may contribute to oligodendrocyte damage and myelin loss in white matter diseases. For some disorders, the mechanisms leading to myelin loss are clear, whereas the aetiological agent and pathological mechanisms are unknown for other myelin disorders, although emerging studies indicate that a common mechanism underlying these disorders is dysregulation of autophagic pathways. In this review we discuss the alterations in the autophagic process in white matter disorders and the potential use of autophagy-modulating agents as therapeutic approaches in these pathological conditions. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.