Selective autophagy receptors in neuronal health and disease

Publication date: Available online 22 October 2019Source: Journal of Molecular BiologyAuthor(s): Owen Conway, Hafize Aysin Akpinar, Vladimir Rogov, Vladimir KirkinAbstractNeurons are electrically excitable, post-mitotic cells that perform sensory, relaying, and motor functions. Because of their unique morphological and functional specialization, cells of this type are sensitive to the stress caused by accumulation of misfolded proteins or damaged organelles. Autophagy is the fundamental mechanism that ensures sequestration of cytosolic material and its subsequent degradation in lysosomes of eukaryotic cells, thereby providing cell-autonomous nutrients and removing harmful cargos. Strikingly, mice and flies lacking functional autophagy develop early-onset progressive neurodegeneration. Like in human neurodegenerative diseases (NDDs) – Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, Huntingtin’s disease, and amyotrophic lateral sclerosis – characteristic protein aggregates observed in autophagy-deficient neurons in the animal models are indicators of the ongoing neuronal pathology. A number of selective autophagy receptors (SARs) have been characterized that interact both with the cargo and components of the autophagic machinery, thus providing the molecular basis for selective degradation of sizable cytosolic components. Interference with autophagy in experimental models, but also during the pathological vagaries in neurons, will thus have far-reac...

Source: Journal of Molecular Biology - October 23, 2019 Category: Molecular Biology Source Type: research