Autophagy in the mammalian nervous system: a primer for neuroscientists

Abstract

Autophagy refers to the lysosomal degradation of damaged or superfluous components and is essential for metabolic plasticity and tissue integrity. This evolutionarily conserved process is particularly vital to mammalian post-mitotic cells such as neurons, which face unique logistical challenges and must sustain homoeostasis over decades. Defective autophagy has pathophysiological importance, especially for human neurodegeneration. The present-day definition of autophagy broadly encompasses two distinct yet related phenomena: non-selective and selective autophagy. In this minireview, we focus on established and emerging concepts in the field, paying particular attention to the physiological significance of macroautophagy and the burgeoning world of selective autophagy pathways in the context of the vertebrate nervous system. By highlighting established basics and recent breakthroughs, we aim to provide a useful conceptual framework for neuroscientists interested in autophagy, in addition to autophagy enthusiasts with an eye on the nervous system.

Emerging roles of ATG7 in human health and disease

“…It is notable that one patient (71 years old) has developed late-onset dementia decline, yet further studies are warranted before this can be attributed to ATG7 deficiency. Despite this, mutations in several genes that participate at multiple steps of autophagy have been implicated in familial neurodegeneration (Menzies et al, 2017;Suomi & McWilliams, 2019). However, there is evidence that the contribution of selective autophagy proteins to neurodegeneration may extend beyond their involvement in selective mechanisms alone.…”

“…Neurodegeneration is characteristic of autophagy‐deficient mouse models, yet the relationship between defective autophagy and human neurodegeneration has been more challenging to reconcile (Suomi & McWilliams, 2019 ). Strong evidence supporting the pathological involvement of autophagy includes the presence of large p62/SQSTM1‐ and ubiquitin‐positive inclusions, hallmarks of autophagy deficiency, in AD, PD and ALS brain tissues (Kuusisto et al , 2001 ; Mizuno et al , 2006 ).…”

“…Despite this, mutations in several genes that participate at multiple steps of autophagy have been implicated in familial neurodegeneration (Menzies et al , 2017 ; Suomi & McWilliams, 2019 ). However, there is evidence that the contribution of selective autophagy proteins to neurodegeneration may extend beyond their involvement in selective mechanisms alone.…”

Natural Compounds and Autophagy: Allies Against Neurodegeneration

“…Unfortunately, major knowledge on the defective autophagy in humans is urgent to successfully treat patients. The importance of preventive or therapeutic autophagy regulation in neurodegenerative diseases is still debated (Bar-Yosef et al, 2019;Maiuri and Kroemer, 2019;Park et al, 2020;Suomi and Mc Williams, 2020). Negrete-Hurtado et al (2020) reported in ATG5 KO mice brain, a non canonical role of ATG proteins and that lipidation machinery is not required for neuronal survival.…”

Neuronal Signaling: A reflection on the Biochemical Society’s newest journal and an exciting outlook on its next steps

“…Finally, we hope this editorial will encourage you to read some of the excellent work being published in Neuronal Signaling [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. Of course, we would welcome any pre-submission queries and look forward to receiving your manuscripts in the future.…”