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      Peganum harmala Extract Has Antiamoebic Activity to Acanthamoeba triangularis Trophozoites and Changes Expression of Autophagy-Related Genes

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          Abstract

          Peganum harmala, a well-known medicinal plant, has been used for several therapeutic purposes as it contains numerous pharmacological active compounds. Our study reported an anti-parasitic activity of P. harmala seed extract against Acanthamoeba triangularis. The stress induced by the extract on the surviving trophozoites for Acanthamoeba encystation and vacuolization was examined by microscopy, and transcriptional expression of Acanthamoeba autophagy-related genes was investigated by quantitative PCR. Our results showed that the surviving trophozoites were not transformed into cysts, and the number of trophozoites with enlarged vacuoles were not significantly different from that of untreated control. Molecular analysis data demonstrated that the mRNA expression of tested AcATG genes, i.e., ATG3, ATG8b, and ATG16, was at a basal level along the treatment. However, upregulation of AcATG16 at 24 h post treatment was observed, which may indicate an autophagic activity of this protein in response to the stress. Altogether, these data revealed the anti- Acanthamoeba activity of P. harmala extract and indicated the association of autophagy mRNA expression and cyst formation under the extract stress, representing a promising plant for future drug development. However, further identification of an active compound and a study of autophagy at the protein level are needed.

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          The machinery of macroautophagy.

          Autophagy is a primarily degradative pathway that takes place in all eukaryotic cells. It is used for recycling cytoplasm to generate macromolecular building blocks and energy under stress conditions, to remove superfluous and damaged organelles to adapt to changing nutrient conditions and to maintain cellular homeostasis. In addition, autophagy plays a critical role in cytoprotection by preventing the accumulation of toxic proteins and through its action in various aspects of immunity including the elimination of invasive microbes and its participation in antigen presentation. The most prevalent form of autophagy is macroautophagy, and during this process, the cell forms a double-membrane sequestering compartment termed the phagophore, which matures into an autophagosome. Following delivery to the vacuole or lysosome, the cargo is degraded and the resulting macromolecules are released back into the cytosol for reuse. The past two decades have resulted in a tremendous increase with regard to the molecular studies of autophagy being carried out in yeast and other eukaryotes. Part of the surge in interest in this topic is due to the connection of autophagy with a wide range of human pathophysiologies including cancer, myopathies, diabetes and neurodegenerative disease. However, there are still many aspects of autophagy that remain unclear, including the process of phagophore formation, the regulatory mechanisms that control its induction and the function of most of the autophagy-related proteins. In this review, we focus on macroautophagy, briefly describing the discovery of this process in mammalian cells, discussing the current views concerning the donor membrane that forms the phagophore, and characterizing the autophagy machinery including the available structural information.
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            Cargo recognition and degradation by selective autophagy

            Macroautophagy, initially described as a non-selective nutrient recycling process, is essential for the removal of multiple cellular components. In the past three decades, selective autophagy has been characterized as a highly regulated and specific degradation pathway for removal of unwanted cytosolic components and damaged and/or superfluous organelles. Here, we discuss different types of selective autophagy, emphasizing the role of ligand receptors and scaffold proteins in providing cargo specificity, and highlight unanswered questions in the field.
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              Most neurodegenerative diseases that afflict humans are associated with the intracytoplasmic deposition of aggregate-prone proteins in neurons and with mitochondrial dysfunction. Autophagy is a powerful process for removing such proteins and for maintaining mitochondrial homeostasis. Over recent years, evidence has accumulated to demonstrate that upregulation of autophagy may protect against neurodegeneration. However, autophagy dysfunction has also been implicated in the pathogenesis of various diseases. This Review summarizes the progress that has been made in our understanding of how perturbations in autophagy are linked with neurodegenerative diseases and the potential therapeutic strategies resulting from the modulation of this process.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Pathogens
                Pathogens
                pathogens
                Pathogens
                MDPI
                2076-0817
                04 July 2021
                July 2021
                : 10
                : 7
                : 842
                Affiliations
                [1 ]Department of Medical Technology, School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80160, Thailand; rachasak.bo@ 123456mail.wu.ac.th (R.B.); mayuna.sr@ 123456wu.ac.th (M.S.); sueptrakool.wi@ 123456wu.ac.th (S.W.)
                [2 ]Research Excellence Center for Innovation and Health Products (RECIHP), School of Allied Health Sciences, Southeast Asia Water Team (SEA Water Team) and World Union for Herbal Drug Discovery (WUHeDD), Walailak University, Nakhon Si Thammarat 80160, Thailand; zillion.nana@ 123456hotmail.com (S.S.); julalak112@ 123456gmail.com (J.C.)
                [3 ]Department of Pathobiology, Faculty of Veterinary Medicine, University of Tabriz, Tabriz 5166616471, Iran; roghayehnorouzi123@ 123456gmail.com
                [4 ]Ferdows School of Paramedical and Health, Birjand University of Medical Sciences, Birjand 9717853577, Iran; asiyadatpanah@ 123456yahoo.com
                [5 ]Department Parasitology and Mycology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd 14188-15971, Iran; mirzaei.farzaneh2015@ 123456yahoo.com
                [6 ]Akkhraratchakumari Veterinary College and Research Center of Excellence in Innovation of Essential Oil, Walailak University, Nakhon Si Thammarat 80160, Thailand; 1234_k@ 123456hotmail.co.th
                [7 ]CICECO-Aveiro Institute of Materials and Department of Medical Sciences, University of Aveiro, 3810-193 Aveiro, Portugal; mlourdespereira@ 123456ua.pt
                [8 ]Department of Biotechnology and Genetic Engineering, University of Development Alternative, Lalmatia, Dhaka 1209, Bangladesh; rahamatm@ 123456hotmail.com
                [9 ]Department of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand
                [10 ]School of Pharmacy, University of Nottingham Malaysia Campus, Selangor 43500, Malaysia; christophe.wiart@ 123456nottingham.edu.my
                [11 ]Division of Applied Biomedical Science and Biotechnology, School of Health Sciences, International Medical University, Kuala Lumpur 57000, Malaysia; chooi_linglim@ 123456imu.edu.my
                [12 ]Department of Microbiology, Sikkim Manipal Institute of Medical Sciences (SMIMS), Sikkim 737102, India; kgdolma@ 123456outlook.com
                Author notes
                Author information
                https://orcid.org/0000-0002-4393-2380
                https://orcid.org/0000-0001-9048-3955
                https://orcid.org/0000-0001-6703-7869
                https://orcid.org/0000-0002-0216-7977
                https://orcid.org/0000-0002-2730-7788
                Article
                pathogens-10-00842
                10.3390/pathogens10070842
                8308471
                1a2d8eb8-775c-462d-8217-8cc83ad408b9
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 08 May 2021
                : 02 July 2021
                Categories
                Article

                peganum harmala,acanthamoeba triangularis,encystation,rt-pcr,autophagy

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