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      Plant-Derived Natural Compounds for the Treatment of Amyotrophic Lateral Sclerosis: An Update

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          Abstract

          Background

          Amyotrophic lateral sclerosis (ALS) is a motor neuron disease (MND) that typically causes death within 3-5 years after diagnosis. Regardless of the substantial scientific knowledge accrued more than a century ago, truly effective therapeutic strategies remain distant. Various conventional drugs are being used but are having several adverse effects.

          Objective/Aim

          The current study aims to thoroughly review plant-derived compounds with well-defined ALS activities and their structure-activity relationships. Moreover, the review also focuses on complex genetics, clinical trials, and the use of natural products that might decrypt the future and novel therapeutics in ALS.

          Methods

          The collection of data for the compilation of this review work was searched in PubMed Scopus, Google Scholar, and Science Direct.

          Results

          Results showed that phytochemicals like-Ginkgolides, Protopanaxatriol, Genistein, epigallocatechingallate, resveratrol, cassoside, and others possess Amyotrophic lateral sclerosis (ALS) activity by various mechanisms.

          Conclusion

          These plant-derived compounds may be considered as supplements for conventional (ALS). Moreover, further preclinical and clinical studies are required to understand the structure-activity relationships, metabolism, absorption, and mechanisms of plant-derived natural agents.

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          Most cited references158

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          Oxidative Stress: A Key Modulator in Neurodegenerative Diseases

          Oxidative stress is proposed as a regulatory element in ageing and various neurological disorders. The excess of oxidants causes a reduction of antioxidants, which in turn produce an oxidation–reduction imbalance in organisms. Paucity of the antioxidant system generates oxidative-stress, characterized by elevated levels of reactive species (oxygen, hydroxyl free radical, and so on). Mitochondria play a key role in ATP supply to cells via oxidative phosphorylation, as well as synthesis of essential biological molecules. Various redox reactions catalyzed by enzymes take place in the oxidative phosphorylation process. An inefficient oxidative phosphorylation may generate reactive oxygen species (ROS), leading to mitochondrial dysfunction. Mitochondrial redox metabolism, phospholipid metabolism, and proteolytic pathways are found to be the major and potential source of free radicals. A lower concentration of ROS is essential for normal cellular signaling, whereas the higher concentration and long-time exposure of ROS cause damage to cellular macromolecules such as DNA, lipids and proteins, ultimately resulting in necrosis and apoptotic cell death. Normal and proper functioning of the central nervous system (CNS) is entirely dependent on the chemical integrity of brain. It is well established that the brain consumes a large amount of oxygen and is highly rich in lipid content, becoming prone to oxidative stress. A high consumption of oxygen leads to excessive production of ROS. Apart from this, the neuronal membranes are found to be rich in polyunsaturated fatty acids, which are highly susceptible to ROS. Various neurodegenerative diseases such as Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), among others, can be the result of biochemical alteration (due to oxidative stress) in bimolecular components. There is a need to understand the processes and role of oxidative stress in neurodegenerative diseases. This review is an effort towards improving our understanding of the pivotal role played by OS in neurodegenerative disorders.
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            Plants as source of drugs.

            This work presents a study of the importance of natural products, especially those derived from higher plants, in terms of drug development. It describes the main strategies for obtaining drugs from natural sources, fields of knowledge involved, difficulties and perspectives. It also includes a brief discussion of the specific situation in Brazil regarding the use of, trade in, and research into therapeutic resources of natural origin and the general lack of awareness of the use of potentially toxic plants, mainly in folk medicine.
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              SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis.

              A progressive loss of neurons with age underlies a variety of debilitating neurological disorders, including Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS), yet few effective treatments are currently available. The SIR2 gene promotes longevity in a variety of organisms and may underlie the health benefits of caloric restriction, a diet that delays aging and neurodegeneration in mammals. Here, we report that a human homologue of SIR2, SIRT1, is upregulated in mouse models for AD, ALS and in primary neurons challenged with neurotoxic insults. In cell-based models for AD/tauopathies and ALS, SIRT1 and resveratrol, a SIRT1-activating molecule, both promote neuronal survival. In the inducible p25 transgenic mouse, a model of AD and tauopathies, resveratrol reduced neurodegeneration in the hippocampus, prevented learning impairment, and decreased the acetylation of the known SIRT1 substrates PGC-1alpha and p53. Furthermore, injection of SIRT1 lentivirus in the hippocampus of p25 transgenic mice conferred significant protection against neurodegeneration. Thus, SIRT1 constitutes a unique molecular link between aging and human neurodegenerative disorders and provides a promising avenue for therapeutic intervention.
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                Author and article information

                Journal
                Curr Neuropharmacol
                Curr Neuropharmacol
                CN
                Current Neuropharmacology
                Bentham Science Publishers
                1570-159X
                1875-6190
                10 January 2022
                10 January 2022
                : 20
                : 1
                : 179-193
                Affiliations
                [1 ]Pharmacognosy & Phytochemistry Division, Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal, Srinagar, 190006, Kashmir, India;
                [2 ]Pharmaceutical Chemistry Division, Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal, Srinagar-190006, Kashmir, India;
                [3 ]Pharmaceutics Division, Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal, Srinagar-190006, Kashmir ,India;
                [4 ]Department of Pharmacognosy, Faculty of Pharmacy, Gazi University , 06330, , Ankara , Turkey;
                [5 ]Department of Pharmacy, Abdul Wali Khan University , Mardan, , 23200 , Pakistan
                Author notes
                [* ]Address correspondence to these authors at the Department of Pharmacy, Faculty of Chemical & Life Sciences, Abdul Wali Khan University Mardan, Pakistan; E-mail: haroonkhan@ 123456awkum.edu.pk , Pharmacognosy & Phytochemistry, Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal, Srinagar, 190006, Kashmir, India; E-mail: zabhat@ 123456kashmiruniversity.ac.in
                [# ] These authors contributed equally to this work.
                Article
                CN-20-179
                10.2174/1570159X19666210428120514
                9199545
                33913406
                011e2272-1b7a-47e7-991a-e65286deb76b
                © 2022 Bentham Science Publishers

                This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) ( https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

                History
                : 03 December 2020
                : 14 March 2021
                : 16 April 2021
                Categories
                Neurology

                Pharmacology & Pharmaceutical medicine
                plant-derived products,sod1 mutations,cns disorders,sar,clinical trials,therapeutic effects

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