Abstract

Autophagy is a process of degradation of macromolecules in the cytoplasm, particularly proteins of a long half-life, as well as whole organelles, in eukaryotic cells. Lysosomes play crucial roles during this degradation. Autophagy is a phylogenetically old, and evolutionarily conserved phenomenon which occurs in all eukaryotic cells. It can be found in yeast Saccharomyces cerevisiae, insect Drosophila melanogaster, and mammals, including humans. Its high importance for cell physiology has been recognized, and in fact, dysfunctions causing impaired autophagy are associated with many severe disorders, including cancer and metabolic brain diseases. The types and molecular mechanisms of autophagy have been reviewed recently by others, and in this paper they will be summarized only briefly. Regulatory networks controlling the autophagy process are usually described as negative regulations. In contrast, here, we focus on different ways by which autophagy can be stimulated. In fact, activation of this process by different factors or processes can be considered as a therapeutic strategy in metabolic neurodegenerative diseases. These aspects are reviewed and discussed in this article.

Highlights

  • Autophagy is a process of degradation of macromolecules in the cytoplasm, proteins of a long half-life, as well as whole organelles, in eukaryotic cells

  • The autophagy facilitates adaptation of the cell to new environmental conditions, as it ensures the availability of compounds necessary for synthesis of macromolecules, required during the stress, through degradation of structures that are less important under such conditions

  • In addition to the above mechanism, due to inactivation of the Akt kinase, the FoxO3 transcription factor is not phosphorylated. It migrates to the nucleus and stimulates expression of genes coding for proteins involved in the autophagy process, i.e. LC3, Vsp34, and ULK1 (Stitt et al 2004)

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Summary

REVIEW ARTICLE

Autophagy stimulation as a promising approach in treatment of neurodegenerative diseases Karolina Pierzynowska1 & Lidia Gaffke1 & Zuzanna Cyske1 & Michał Puchalski1 & Estera Rintz1 & Michał Bartkowski1 & Marta Osiadły1 & Michał Pierzynowski1 & Jagoda Mantej1 & Ewa Piotrowska1 & Grzegorz Węgrzyn. Received: 10 January 2018 / Accepted: 8 March 2018 / Published online: 14 March 2018 # The Author(s) 2018

The autophagy process
The role of autophagy in the cell
Molecular mechanism of autophagy
Nucleation and elongation
Fusion of autophagosome with lysosome
Lysosomal degradation
Autophagy activation pathways
Inositol signaling pathway
Cause of disease
Calcium canal antagonists
Valproic acid
Concluding remarks
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