Abstract
Autophagy modulation is considered to be a promising programmed cell death mechanism to prevent and cure a great number of disorders and diseases. The crucial step in designing an effective therapeutic approach is to understand the correct and accurate causes of diseases and to understand whether autophagy plays a cytoprotective or cytotoxic/cytostatic role in the progression and prevention of disease. This knowledge will help scientists find approaches to manipulate tumor and pathologic cells in order to enhance cellular sensitivity to therapeutics and treat them. Although some conventional therapeutics suffer from poor solubility, bioavailability and controlled release mechanisms, it appears that novel nanoplatforms overcome these obstacles and have led to the design of a theranostic-controlled drug release system with high solubility and active targeting and stimuli-responsive potentials. In this review, we discuss autophagy modulators-related signaling pathways and some of the drug delivery strategies that have been applied to the field of therapeutic application of autophagy modulators. Moreover, we describe how therapeutics will target various steps of the autophagic machinery. Furthermore, nano drug delivery platforms for autophagy targeting and co-delivery of autophagy modulators with chemotherapeutics/siRNA, are also discussed.
Highlights
Autophagy—cell self-digestion machinery—is a substantial process which plays critical roles in many cellular processes and functions
We describe the basics of autophagy with an emphasis on the molecular signaling pathways and demonstrate that how nanocarriers can aid in enhancing the efficacy of autophagy modulators
AMPK Signaling Pathway and Autophagy. Eukaryotes modulate their metabolism through adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway as an evolved system based on their nutrient availability
Summary
Autophagy—cell self-digestion machinery—is a substantial process which plays critical roles in many cellular processes and functions. An important point is related to the modulatory effect of autophagy on immune system where elevated autophagy in advanced cancers increases high-mobility group box 1 protein (HMGB1) release [28] These events result in inducing anti-tumor T-cell responses through the activation of Toll-like receptors. The interesting point is related to the enabling autophagy at the basal level even if there are sufficient nutrients and energy in the cell in order to remove damaged organelles as well as aggregated or misfolded macromolecules Due to their inhibitory role of autophagy initiation, mTORC inhbitors/activators have been extensively studied for their autophagy modulating effects and therapeutic application. It appears that endosome pool has the major role in suppressing macroatuophagy and microautophagy by phosphorylation of Atg and Vps, respectively, while vacuole pool contributes to enhancing the translation [58,59]
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