scholarly journals Potential of Naturally Derived Alkaloids as Multi-Targeted Therapeutic Agents for Neurodegenerative Diseases

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 728
Author(s):  
Yew Rong Kong ◽  
Kai Ching Tay ◽  
Yi Xiang Su ◽  
Choon Kwang Wong ◽  
Wen Nee Tan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chronic Disease ◽  
Secondary Metabolites ◽  
Neurodegenerative Diseases ◽  
Therapeutic Agents ◽  
Marine Sponges ◽  
Huperzine A ◽  
Symptomatic Management ◽  
Recent Developments ◽  
Continuous Source

Alkaloids are a class of secondary metabolites that can be derived from plants, fungi and marine sponges. They are widely known as a continuous source of medicine for the management of chronic disease including cancer, diabetes and neurodegenerative diseases. For example, galanthamine and huperzine A are alkaloid derivatives currently being used for the symptomatic management of neurodegenerative disease. The etiology of neurodegenerative diseases is polygenic and multifactorial including but not limited to inflammation, oxidative stress and protein aggregation. Therefore, natural-product-based alkaloids with polypharmacology modulation properties are potentially useful for further drug development or, to a lesser extent, as nutraceuticals to manage neurodegeneration. This review aims to discuss and summarise recent developments in relation to naturally derived alkaloids for neurodegenerative diseases.

scholarly journals The Role of NADPH Oxidases and Oxidative Stress in Neurodegenerative Disorders

2018 ◽  
Vol 19 (12) ◽  
pp. 3824 ◽  
Author(s):  
Anuradha Tarafdar ◽  
Giordano Pula
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Ros Generation ◽  
Phagocytic Cells ◽  
Nadph Oxidases ◽  
Age Related ◽  
Recent Developments ◽  
Cerebrovascular Endothelial Cells

For a number of years, nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX) was synonymous with NOX2/gp91phox and was considered to be a peculiarity of professional phagocytic cells. Over the last decade, several more homologs have been identified and based on current research, the NOX family consists of NOX1, NOX2, NOX3, NOX4, NOX5, DUOX1 and DUOX2 enzymes. NOXs are electron transporting membrane proteins that are responsible for reactive oxygen species (ROS) generation—primarily superoxide anion (O2●−), although hydrogen peroxide (H2O2) can also be generated. Elevated ROS leads to oxidative stress (OS), which has been associated with a myriad of inflammatory and degenerative pathologies. Interestingly, OS is also the commonality in the pathophysiology of neurodegenerative disorders, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). NOX enzymes are expressed in neurons, glial cells and cerebrovascular endothelial cells. NOX-mediated OS is identified as one of the main causes of cerebrovascular damage in neurodegenerative diseases. In this review, we will discuss recent developments in our understanding of the mechanisms linking NOX activity, OS and neurodegenerative diseases, with particular focus on the neurovascular component of these conditions. We conclude highlighting current challenges and future opportunities to combat age-related neurodegenerative disorders by targeting NOXs.

scholarly journals Signaling, Polyubiquitination, Trafficking, and Inclusions: Sequestosome 1/p62's Role in Neurodegenerative Disease

2006 ◽  
Vol 2006 ◽  
pp. 1-12 ◽  
Author(s):  
Marie W. Wooten ◽  
Xiao Hu ◽  
J. Ramesh Babu ◽  
M. Lamar Seibenhener ◽  
Thangiah Geetha ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Chronic Disease ◽  
Neurodegenerative Diseases ◽  
Inclusion Formation ◽  
Disease Biomarker ◽  
Sequestosome 1 ◽  
Uba Domain ◽  
Chronic Disease State

Aggregated misfolded proteins are hallmarks of most neurodegenerative diseases. In a chronic disease state, including pathologic situations of oxidative stress, these proteins are sequestered into inclusions. Accumulation of aggregated proteins can be prevented by chaperones, or by targeting their degradation to the UPS. If the accumulation of these proteins exceeds their degradation, they may impair the function of the proteasome. Alternatively, the function of the proteasome may be preserved by directing aggregated proteins to the autophagy-lysosome pathway for degradation. Sequestosome 1/p62 has recently been shown to interact with polyubiquitinated proteins through its UBA domain and may direct proteins to either the UPS or autophagosome. P62 is present in neuronal inclusions of individuals with Alzheimer's disease and other neurodegenerative diseases. Herein, we review p62's role in signaling, aggregation, and inclusion formation, and specifically as a possible contributor to Alzheimer's disease. The use of p62 as a potential target for the development of therapeutics and as a disease biomarker is also discussed.

scholarly journals Recent Developments in the Reduction of Oxidative Stress through Antioxidant Polymeric Formulations

Pharmaceutics ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 505 ◽  
Author(s):  
Zafar ◽  
Quarta ◽  
Marradi ◽  
Ragusa
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Cigarette Smoke ◽  
Detrimental Effect ◽  
Sunlight Exposure ◽  
External Factors ◽  
Nitrogen Species ◽  
Natural Extracts ◽  
Pathological Conditions ◽  
Recent Developments

Reactive oxygen and nitrogen species (RONS) are produced endogenously in our body, or introduced through external factors, such as pollution, cigarette smoke, and excessive sunlight exposure. In normal conditions, there is a physiological balance between pro-oxidant species and antioxidant molecules that are able to counteract the detrimental effect of the former. Nevertheless, when this homeostasis is disrupted, the resulting oxidative stress can lead to several pathological conditions, from inflammation to cancer and neurodegenerative diseases. In this review, we report on the recent developments of different polymeric formulations that are able to reduce the oxidative stress, from natural extracts, to films and hydrogels, and finally to nanoparticles (NPs).

scholarly journals Recent Advances in the Treatment of Neurodegenerative Diseases Based on GSH Delivery Systems

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Ivana Cacciatore ◽  
Leonardo Baldassarre ◽  
Erika Fornasari ◽  
Adriano Mollica ◽  
Francesco Pinnen
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Therapeutic Agents ◽  
Brain Cell ◽  
Cell Populations ◽  
Specific Loss ◽  
Dna And Rna ◽  
The Central Nervous System ◽  
Gsh Metabolism ◽  
Poor Stability

Neurodegenerative diseases, such as Parkinson's disease (PD) and Alzheimer's disease(AD), are a group of pathologies characterized by a progressive and specific loss of certain brain cell populations. Oxidative stress, mitochondrial dysfunction, and apoptosis play interrelated roles in these disorders. It is well documented that free radical oxidative damage, particularly on neuronal lipids, proteins, DNA, and RNA, is extensive in PD and AD brains. Moreover, alterations of glutathione (GSH) metabolism in brain have been implicated in oxidative stress and neurodegenerative diseases. As a consequence, the reduced GSH levels observed in these pathologies have stimulated a number of researchers to find new potential approaches for maintaining or restoring GSH levels. Unfortunately, GSH delivery to the central nervous system (CNS) is limited due to a poor stability and low bioavailability. Medicinal-chemistry- and technology-based approaches are commonly used to improve physicochemical, biopharmaceutical, and drug delivery properties of therapeutic agents. This paper will focus primarily on these approaches used in order to replenish intracellular GSH levels, which are reduced in neurodegenerative diseases. Here, we discuss the beneficial properties of these approaches and their potential implications for the future treatment of patients suffering from neurodegenerative diseases, and more specifically from PD and AD.

scholarly journals Effects of Polyphenols on Oxidative Stress, Inflammation, and Interconnected Pathways during Spinal Cord Injury

2022 ◽  
Vol 2022 ◽  
pp. 1-34
Author(s):  
Sajad Fakhri ◽  
Fatemeh Abbaszadeh ◽  
Seyed Zachariah Moradi ◽  
Hui Cao ◽  
Haroon Khan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Secondary Metabolites ◽  
Potential Role ◽  
Therapeutic Agents ◽  
Cord Injury ◽  
Potential Alternative ◽  
Preclinical And Clinical Studies

Despite the progression in targeting the complex pathophysiological mechanisms of neurodegenerative diseases (NDDs) and spinal cord injury (SCI), there is a lack of effective treatments. Moreover, conventional therapies suffer from associated side effects and low efficacy, raising the need for finding potential alternative therapies. In this regard, a comprehensive review was done regarding revealing the main neurological dysregulated pathways and providing alternative therapeutic agents following SCI. From the mechanistic point, oxidative stress and inflammatory pathways are major upstream orchestras of cross-linked dysregulated pathways (e.g., apoptosis, autophagy, and extrinsic mechanisms) following SCI. It urges the need for developing multitarget therapies against SCI complications. Polyphenols, as plant-derived secondary metabolites, have the potential of being introduced as alternative therapeutic agents to pave the way for treating SCI. Such secondary metabolites presented modulatory effects on neuronal oxidative stress, neuroinflammatory, and extrinsic axonal dysregulated pathways in the onset and progression of SCI. In the present review, the potential role of phenolic compounds as critical phytochemicals has also been revealed in regulating upstream dysregulated oxidative stress/inflammatory signaling mediators and extrinsic mechanisms of axonal regeneration after SCI in preclinical and clinical studies. Additionally, the coadministration of polyphenols and stem cells has shown a promising strategy for improving post-SCI complications.

Pigments from Filamentous Ascomycetes for Combination Therapy

2019 ◽  
Vol 26 (20) ◽  
pp. 3812-3834
Author(s):  
Róbert Hromádka ◽  
Zdeněk Kejík ◽  
Milan Jakubek ◽  
Robert Kaplánek ◽  
Viera Šandriková ◽  
...  
Keyword(s):  
Side Effects ◽  
Secondary Metabolites ◽  
Combination Therapy ◽  
Neurodegenerative Diseases ◽  
Potential Application ◽  
Therapeutic Efficacy ◽  
Therapeutic Agents ◽  
Oncological Diseases ◽  
Long Time ◽  
Future Potential

Filamentous ascomycetes (Neurospora and Monascus) have been studied for a long time because of their production of secondary metabolites such as microbial pigments. The ascomycetes represent an interesting group of compounds with high potential for medicinal applications. Many recent studies have shown their efficacy in the treatment of serious pathological states such as oncological diseases, neurodegenerative diseases and hyperlipidaemia. Nevertheless, the clinical usability of ascomycetes is still limited. However, this problem can be solved by the use of these compounds with combinations of other therapeutic agents. This strategy can suppress their side effects and improve their therapeutic efficacy. Moreover, their co-application can significantly enhance conventional therapies that are used. This review summarizes and discusses the general principles of this approach, introduced and supported by numerous examples. In addition, the prediction of the future potential application of this methodology is included.

scholarly journals Recent Updates in the Treatment of Neurodegenerative Disorders Using Natural Compounds

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Mahmood Rasool ◽  
Arif Malik ◽  
Muhammad Saeed Qureshi ◽  
Abdul Manan ◽  
Peter Natesan Pushparaj ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Side Effects ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Therapeutic Agents ◽  
Chronic Illnesses ◽  
Biological Processes ◽  
Brain Disorders ◽  
Synthetic Drugs ◽  
The Central Nervous System

Neurodegenerative diseases are characterized by protein aggregates and inflammation as well as oxidative stress in the central nervous system (CNS). Multiple biological processes are linked to neurodegenerative diseases such as depletion or insufficient synthesis of neurotransmitters, oxidative stress, abnormal ubiquitination. Furthermore, damaging of blood brain barrier (BBB) in the CNS also leads to various CNS-related diseases. Even though synthetic drugs are used for the management of Alzheimer’s disease, Parkinson’s disease, autism, and many other chronic illnesses, they are not without side effects. The attentions of researchers have been inclined towards the phytochemicals, many of which have minimal side effects. Phytochemicals are promising therapeutic agents because many phytochemicals have anti-inflammatory, antioxidative as well as anticholinesterase activities. Various drugs of either synthetic or natural origin applied in the treatment of brain disorders need to cross the BBB before they can be used. This paper covers various researches related to phytochemicals used in the management of neurodegenerative disorders.

Lycopene alleviates sulfamethoxazole-induced hepatotoxicity in grass carp (Ctenopharyngodon idellus) via suppression of oxidative stress, inflammation and apoptosis

2020 ◽  
Vol 11 (10) ◽  
pp. 8547-8559
Author(s):  
Hongjing Zhao ◽  
Yu Wang ◽  
Mengyao Mu ◽  
Menghao Guo ◽  
Hongxian Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Secondary Metabolites ◽  
Human Health ◽  
Grass Carp ◽  
Aquatic Environment ◽  
Ctenopharyngodon Idellus

Antibiotics are used worldwide to treat diseases in humans and other animals; most of them and their secondary metabolites are discharged into the aquatic environment, posing a serious threat to human health.

Oxidative Stress and Neurodegenerative Diseases: Looking for a Therapeutic Solution Inspired on Benzopyran Chemistry

2015 ◽  
Vol 15 (5) ◽  
pp. 432-445 ◽  
Author(s):  
Alexandra Gaspar ◽  
Nuno Milhazes ◽  
Lourdes Santana ◽  
Eugenio Uriarte ◽  
Fernanda Borges ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases
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