Therapeutic Implications of Autophagy (original) (raw)

Autophagy Intertwines with Different Diseases-Recent Strategies for Therapeutic Approaches

Multidisciplinary Digital Publishing Institute-Diseases, 2019

Autophagy is a regular and substantial “clear-out process” that occurs within the cell and that gets rid of debris that accumulates in membrane-enclosed vacuoles by using enzyme-rich lysosomes, which are filled with acids that degrade the contents of the vacuoles. This machinery is well-connected with many prevalent diseases, including cancer, HIV, and Parkinson’s disease. Considering that autophagy is well-known for its significant connections with a number of well-known fatal diseases, a thorough knowledge of the current findings in the field is essential in developing therapies to control the progression rate of diseases. Thus, this review summarizes the critical events comprising autophagy in the cellular system and the significance of its key molecules in manifesting this pathway in various diseases for down-or upregulation. We collectively reviewed the role of autophagy in various diseases, mainly neurodegenerative diseases, cancer, inflammatory diseases, and renal disorders. Here, some collective reports on autophagy showed that this process might serve as a dual performer: either protector or contributor to certain diseases. The aim of this review is to help researchers to understand the role of autophagy-regulating genes encoding functional open reading frames (ORFs) and its connection with diseases, which will eventually drive better understanding of both the progression and suppression of different diseases at various stages. This review also focuses on certain novel therapeutic strategies which have been published in the recent years based on targeting autophagy key proteins and its interconnecting signaling cascades

Therapeutic implications of autophagy in cancer treatment

2019

Autophagy is a survival process in which a cell preserves its own components in case of nutrient deprivation by recycling its digested contents and cannibalizing itself. It is characterized by the double membrane autophagosomes formation and it has a fantastic role in cancer treatment by many mechanisms. Interestingly, Autophagy has a great effect in the treatment of many diseases by different mechanisms. Autophagy has been included as a treatment mechanism of various diseases by cell losing, such as degenerative diseases of the muscle and nervous system. It has been found abundant of autophagic vacuoles inside the damaged cells in many of these degenerative disorders. Autophagy can help both living cells and cancer cells to survive so when the strategy of the treatment of cancer decreases autophagy process of cancer cells, it prevents them to survive and divide. In this review, we illustrated the definition of autophagy, autophagic pathways, therapeutic implications of autophagy, t...

Review on Autophagy: Mechanism of Cell House Keeping

2018

Autophagy is a normal process occurring in our body to maintain cellular homeostasis but it is up-regulated during stress condition inside the cell. It is a highly conserved and regulated process which involves lysosomal mediated degradation of damaged and faulty components and recycle or reuses when needed. Despite its role in degradation it has its connection with various diseases like cancer, neurodegeneration, muscle disease, liver disease, cardiac disease and many more. The process of autophagy consist of various steps and each step is regulated by various regulatory proteins which is found to be deleted or mutated when present in disease. This review has focus on the process of autophagy and its regulation along with its connection with various diseases. Few examples might be paving a way for innovative remedy for treating many diseases

Autophagy modulation as a potential therapeutic target for diverse diseases

Nature Reviews Drug Discovery, 2012

Autophagy is an essential, conserved lysosomal degradation pathway that controls the quality of the cytoplasm by eliminating protein aggregates and damaged organelles. It begins when doublemembraned autophagosomes engulf portions of the cytoplasm, which is followed by fusion of these vesicles with lysosomes and degradation of the autophagic contents. In addition to its vital homeostatic role, this degradation pathway is involved in various human disorders, including metabolic conditions, neurodegenerative diseases, cancers and infectious diseases. This article provides an overview of the mechanisms and regulation of autophagy, the role of this pathway in disease and strategies for therapeutic modulation.

Therapeutic implications of autophagy in cancer treatment Arabian Journal of Medical Sciences

Article Info Autophagy is a survival process in which a cell preserves its components in case of nutrient deprivation by recycling its digested contents and cannibalizing itself. It is characterized by formation of double membrane autophagosomes and it has a role in cancer treatment by many mechanisms. Interestingly, autophagy has a significant effect in the treatment of many diseases by different mechanisms. Autophagy has been included as a treatment mechanism of various diseases, such as degenerative diseases of the muscle and nervous system. Abundant autophagic vacuoles were formed inside the damaged cells in many of these degenerative disorders. Autophagy can help both living cells and cancer cells to survive so some antitumor agents targeted autophagy in cancer cells. In this review, we illustrated the definition of autophagy, autophagic pathways, therapeutic implications of autophagy in cancer, the relationship between autophagy and cell death, inflammation, and necrosis.

Autophagy in health and disease. 1. Regulation and significance of autophagy: an overview

AJP: Cell Physiology, 2010

The autophagosome is the central organelle in macroautophagy, a vacuolar lysosomal catabolic pathway by which cytoplasmic material is degraded to fuel cells subjected to starvation, via which intracellular pathogens are eliminated. Macroautophagy plays important physiological roles during development, ageing, and the immune response, and the cytoprotective function of macroautophagy is compromised in diseases such as cancer, neurodegenerative disorders, and diabetes. A set of autophagy-related (ATG) proteins is hierarchically recruited to the phagophore, the initial membrane template in the construction of the autophagosome. However, recent findings suggest that macroautophagy can also occur without some of these key autophagy proteins, and such alternatives to the evolutionarily-conserved scheme might provide additional opportunities for therapeutic intervention.

Autophagy stimulation as a promising approach in treatment of neurodegenerative diseases

Metabolic brain disease, 2018

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, activa...

Role of autophagy and its significance in cellular homeostasis

Applied Microbiology and Biotechnology, 2014

Autophagy is a catabolic pathway that regulates homeostasis in cells. It is an exceptional pathway of membrane trafficking. Autophagy is characterized by the formation of double-membrane vesicles; autophagosomes that are responsible for delivering damaged organelle and extra proteins to lysosome for recycling. A series of actions including environmental and genetic factors are responsible for induction of autophagy. In the past few decades, the research on autophagy has been immensely expanded because it is a vital process in maintaining cellular balance as well as deeply connected with pathogenesis of a number of diseases. The aim of this review is to present an overview of modern work on autophagy and highlight some essential genetic role in the induction of autophagy. There is an emerging need to identify, quantify, and manipulate the pathway of autophagy, due to its close relationship with a variety of developmental pathways and functions especially in cancer, diabetes, neurodegenerative disorders, and infectious diseases.

An overview on the role of autophagy in cancer therapy

Hematology & Medical Oncology, 2017

Autophagy is a highly regulated catabolic process through which cells recycle their own constituents by delivering them into lysosomes. Several studies have demonstrated that autophagy plays a wide variety of physiological and pathophysiological roles in cells. In cancer, autophagy has been described to have paradoxical roles, acting both as tumor suppressor and as tumor promoter. In particular, it may exert different functions in response to cancer therapy, causing cancer resistance or increasing sensitivity to chemotherapeutic drugs and radiation. Therefore, autophagy could provide new means for the enhancement of antitumor drugs and radiation effectiveness.