Autophagy in childhood neurological disorders

Abstract

Autophagy is a tightly modulated lysosomal degradation pathway. Genetic disorders of autophagy during nervous system development may lead to developmental delay, neurodegeneration, and other neurological signs in children. Here we aimed to summarize single gene disorders that perturb various steps of autophagy pathway and their roles in the causation of childhood neurological diseases. Numerous childhood‐onset disorders are caused by mutations that impact the autophagy pathway. These can manifest with a range of features including ataxia, spastic paraplegia, and intellectual disability. Defective proteins causing such diseases can interfere with autophagy flux at different stages of the itinerary. Defective autophagy may be an important contributor to the pathological features of various childhood neurodegenerative diseases and lead to the accumulation of aberrant protein and dysfunctional organelles. Insights into the relevant cell biological processes may help understand pathophysiological mechanisms and inspire autophagy‐restoring therapeutic approaches. What this paper adds Numerous childhood‐onset disorders are caused by mutations that impact the autophagy pathway. Defective autophagy is a feature of some mutations that cause ataxia, spastic paraplegia, and intellectual disability.

β8 Integrin Mediates Pancreatic Cancer Cell Radiochemoresistance

“…These findings are in line with published work describing high levels of basal autophagy and macropinocytosis arising from intense metabolic rewiring (35). Although the various proteins found in the b8 integrin interactome also require further attention to unravel the underlying mechanism, some are already well-known determinants of the autophagy process such as RHEB (36,37), DNAJB1 (38), FKBP1A (39), and HADHA (40). Importantly, we observed increasing interactions of these autophagy-associated proteins with b8 integrin upon radiogenic genotoxic stress.…”

Autophagy in childhood neurological disorders

“…In the version of this article originally published in print and online, there was an error in the second affiliation of David C Rubinsztein. It read ‘UK Dementia Research Institute, Wellcome Trust, Cambridge Biomedical Campus, Cambridge, UK’ but should have read ‘UK Dementia Research Institute, Cambridge Biomedical Campus, Cambridge, UK’.…”