The paper reviewed here is ‘Autophagy in Neurodegeneration and Development’ by Winslow and Rubinsztein and freely available here. As the title suggests, the authors discuss the role of autophagy in neurodevelopment and neurodegeneration. As in a number of other review articles that have been discussed here, there is no stated methodology although such articles represent an effective method of communicating important areas that have been selected based on the authors expertise. The paper is divided into 9 sections. In the first section the authors introduce the reader to the two main degradation pathways for proteins in the cell – the specific ubiquitin-proteosome pathway and the non-specific autophagy-lysosome pathway. In the second section they examine Yeast studies. I was intrigued to read that autophagy is induced during periods of starvation in Yeast. The authors summarise the main steps in autophagy that have been identified from Yeast studies. In the third section, the role of autophagy in development and health is examined and again the authors show the important role that autophagy plays in the stress response and deficiencies in components of the pathway can lead to neurodegeneration through the build up of proteins and the lack of nutrients derived from amino-acids. In the fourth section, the authors look at the interactions with other cellular processes and the impact this can have on autophagy proposing that
‘A number of diseases have been shown to manifest a deficiency in autophagy, identifying autophagy as an important secondary disease mechanism‘
In the fifth section, the motor function of dynein in autophagy is discussed as well as the association of under or over-representation of dynein with neurodegeneration which is possibly mediated through impaired autophagy. In the sixth section, the endosomal sorting complexes required for transport (ESCRT for short) are discussed including their association with Frontotemporal Dementia and their role in the processing of integral membrane proteins. In the seventh section, the role of the lysosome in degrading the cargo of the autophagosomes is examined as well as the pathological accumulation of autophagosomes. In the eighth section, there is a look at potential therapeutic interventions aimed at the autophagy pathway and in this regards they consider Rapamycin and intriguingly also Lithium as well as Carbamezapine and Valproate before concluding in the final section that
‘With its implicated roles ranging from viral infection and cancer to liver and cardiac disease.. autophagy’s importance in the maintenance of health is just beginning to be realised‘
The authors have written a review which is elegant in its simplicity and efficacy in communicating the significance of complex cellular processes with many pieces of the ‘jigsaw’ still missing. The authors have also shown the potential relevance of this system to a number of neurodegenerative processes.
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