Impact of Non-Enzymatic Glycation in Neurodegenerative Diseases: Role of Natural Products in Prevention

Limonene is a monoterpene confined to the family of Rutaceae, showing several biological properties such as antioxidant, anti-inflammatory, anticancer, antinociceptive and gastroprotective characteristics. Recently, there is notable interest in investigating the pharmacological effects of limonene in various chronic diseases due to its mitigating effect on oxidative stress and inflammation and regulating apoptotic cell death. There are several available studies demonstrating the neuroprotective role of limonene in neurodegenerative diseases, including Alzheimer’s disease, multiple sclerosis, epilepsy, anxiety, and stroke. The high abundance of limonene in nature, its safety profile, and various mechanisms of action make this monoterpene a favorable molecule to be developed as a nutraceutical for preventive purposes and as an alternative agent or adjuvant to modern therapeutic drugs in curbing the onset and progression of neurodegenerative diseases. This manuscript presents a comprehensive review of the available scientific literature discussing the pharmacological activities of limonene or plant products containing limonene which attribute to the protective and therapeutic ability in neurodegenerative disorders. This review has been compiled based on the existing published articles confined to limonene or limonene-containing natural products investigated for their neurotherapeutic or neuroprotective potential. All the articles available in English or the abstract in English were extracted from different databases that offer an access to diverse journals. These databases are PubMed, Scopus, Google Scholar, and Science Direct. Collectively, this review emphasizes the neuroprotective potential of limonene against neurodegenerative and other neuroinflammatory diseases. The available data are indicative of the nutritional use of products containing limonene and the pharmacological actions and mechanisms of limonene and may direct future preclinical and clinical studies for the development of limonene as an alternative or complementary phytomedicine. The pharmacophore can also provide a blueprint for further drug discovery using numerous drug discovery tools.

Download Full-text

The Role of Reactive Oxygen Species in the Pathogenesis of Alzheimer’s Disease, Parkinson’s Disease, and Huntington’s Disease: A Mini Review

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/8590578 ◽

2016 ◽

Vol 2016 ◽

pp. 1-15 ◽

Cited By ~ 151

Author(s):

Shanmugam Manoharan ◽

Gilles J. Guillemin ◽

Rajagopal Selladurai Abiramasundari ◽

Musthafa Mohamed Essa ◽

Mohammed Akbar ◽

...

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Parkinson’S Disease ◽

Alzheimer's Disease ◽

Parkinson's Disease ◽

Natural Products ◽

Neurodegenerative Diseases ◽

Huntington's Disease ◽

Huntington’S Disease

Neurodegenerative diseases affect not only the life quality of aging populations, but also their life spans. All forms of neurodegenerative diseases have a massive impact on the elderly. The major threat of these brain diseases includes progressive loss of memory, Alzheimer’s disease (AD), impairments in the movement, Parkinson’s disease (PD), and the inability to walk, talk, and think, Huntington’s disease (HD). Oxidative stress and mitochondrial dysfunction are highlighted as a central feature of brain degenerative diseases. Oxidative stress, a condition that occurs due to imbalance in oxidant and antioxidant status, has been known to play a vital role in the pathophysiology of neurodegenerative diseases including AD, PD, and HD. A large number of studies have utilized oxidative stress biomarkers to investigate the severity of these neurodegenerative diseases and medications are available, but these only treat the symptoms. In traditional medicine, a large number of medicinal plants have been used to treat the symptoms of these neurodegenerative diseases. Extensive studies scientifically validated the beneficial effect of natural products against neurodegenerative diseases using suitable animal models. This short review focuses the role of oxidative stress in the pathogenesis of AD, PD, and HD and the protective efficacy of natural products against these diseases.

Download Full-text

Natural Products as Modulators of the Proteostasis Machinery: Implications in Neurodegenerative Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms20194666 ◽

2019 ◽

Vol 20 (19) ◽

pp. 4666 ◽

Cited By ~ 1

Author(s):

Karina Cuanalo-Contreras ◽

Ines Moreno-Gonzalez

Keyword(s):

Natural Products ◽

Neurodegenerative Diseases ◽

Protein Quality ◽

Biological Function ◽

Current Knowledge ◽

Three Dimensional ◽

Protein Homeostasis ◽

Primary Role ◽

Damage Protein

Proteins play crucial and diverse roles within the cell. To exert their biological function they must fold to acquire an appropriate three-dimensional conformation. Once their function is fulfilled, they need to be properly degraded to hamper any possible damage. Protein homeostasis or proteostasis comprises a complex interconnected network that regulates different steps of the protein quality control, from synthesis and folding, to degradation. Due to the primary role of proteins in cellular function, the integrity of this network is critical to assure functionality and health across lifespan. Proteostasis failure has been reported in the context of aging and neurodegeneration, such as Alzheimer’s and Parkinson’s disease. Therefore, targeting the proteostasis elements emerges as a promising neuroprotective therapeutic approach to prevent or ameliorate the progression of these disorders. A variety of natural products are known to be neuroprotective by protein homeostasis interaction. In this review, we will focus on the current knowledge regarding the use of natural products as modulators of different components of the proteostasis machinery within the framework of age-associated neurodegenerative diseases.

Download Full-text

Role of the Structural Characteristics of Dendrimers in the Manifestation of the Antiamyloid Properties

INEOS OPEN ◽

10.32931/io2018r ◽

2020 ◽

Vol 3 ◽

Author(s):

S. A. Sorokina ◽

◽

Yu. Yu. Stroilova ◽

V. I. Muronets ◽

Z. B. Shifrina ◽

...

Keyword(s):

Neurodegenerative Diseases ◽

Structural Characteristics ◽

Short Review ◽

External Factors ◽

Amyloid Aggregation ◽

Amyloid Proteins ◽

Molecular Parameters ◽

Amyloid Aggregates ◽

Aggregation Processes

Among the compounds able to efficiently inhibit the amyloid aggregation of proteins and decompose the amyloid aggregates that cause neurodegenerative diseases, of particular interest are dendrimers, which represent individual macromolecules with the hypercrosslinked architectures and given molecular parameters. This short review outlines the peculiarities of the antiamyloid activity of dendrimers and discusses the effect of dendrimer structures and external factors on their antiamyloid properties. The potential of application of dendrimers in further investigations on the aggregation processes of amyloid proteins as the compounds that exhibit the remarkable antiamyloid activity is evaluated.

Download Full-text

The Role of Advanced Glycation End Products (AGEs) through the TRPA-1/NRF-2 Activation Pathway in the Neurodegenerative Diseases

10.33015/dominican.edu/2017.bio.05 ◽

2017 ◽

Author(s):

Sana Khateeb

Keyword(s):

Neurodegenerative Diseases ◽

Advanced Glycation End Products ◽

Advanced Glycation ◽

Activation Pathway ◽

Glycation End Products ◽

End Products

Download Full-text

Natural Products for the Treatment of Neurodegenerative Diseases

Current Medicinal Chemistry ◽

10.2174/0929867326666190527120614 ◽

2020 ◽

Vol 27 (34) ◽

pp. 5790-5828 ◽

Cited By ~ 1

Author(s):

Ze Wang ◽

Chunyang He ◽

Jing-Shan Shi

Keyword(s):

Nervous System ◽

Natural Products ◽

Neurodegenerative Diseases ◽

Neuroprotective Effect ◽

Rapid Development ◽

New Drugs ◽

Progressive Degeneration ◽

Cord Injury ◽

The Central Nervous System ◽

And Function

Neurodegenerative diseases are a heterogeneous group of disorders characterized by the progressive degeneration of the structure and function of the central nervous system or peripheral nervous system. Alzheimer's Disease (AD), Parkinson's Disease (PD) and Spinal Cord Injury (SCI) are the common neurodegenerative diseases, which typically occur in people over the age of 60. With the rapid development of an aged society, over 60 million people worldwide are suffering from these uncurable diseases. Therefore, the search for new drugs and therapeutic methods has become an increasingly important research topic. Natural products especially those from the Traditional Chinese Medicines (TCMs), are the most important sources of drugs, and have received extensive interest among pharmacist. In this review, in order to facilitate further chemical modification of those useful natural products by pharmacists, we will bring together recent studies in single natural compound from TCMs with neuroprotective effect.

Download Full-text

Involvement of Heme Oxygenase-1 in Neuropsychiatric and Neurodegenerative Diseases

Current Pharmaceutical Design ◽

10.2174/1381612824666180717160623 ◽

2018 ◽

Vol 24 (20) ◽

pp. 2283-2302 ◽

Cited By ~ 9

Author(s):

Vivian B. Neis ◽

Priscila B. Rosa ◽

Morgana Moretti ◽

Ana Lucia S. Rodrigues

Keyword(s):

Neurodegenerative Diseases ◽

Heme Oxygenase ◽

Therapeutic Potential ◽

Redox Homeostasis ◽

Antioxidant Defenses ◽

Heme Oxygenase 1 ◽

Physiological Conditions ◽

And Oxidative Stress ◽

Defensive Mechanism

Heme oxygenase (HO) family catalyzes the conversion of heme into free iron, carbon monoxide and biliverdin. It possesses two well-characterized isoforms: HO-1 and HO-2. Under brain physiological conditions, the expression of HO-2 is constitutive, abundant and ubiquitous, whereas HO-1 mRNA and protein are restricted to small populations of neurons and neuroglia. HO-1 is an inducible enzyme that has been shown to participate as an essential defensive mechanism for neurons exposed to oxidant challenges, being related to antioxidant defenses in certain neuropathological conditions. Considering that neurodegenerative diseases (Alzheimer’s Disease (AD), Parkinson’s Disease (PD) and Multiple Sclerosis (MS)) and neuropsychiatric disorders (depression, anxiety, Bipolar Disorder (BD) and schizophrenia) are associated with increased inflammatory markers, impaired redox homeostasis and oxidative stress, conditions that may be associated with alterations in HO-levels/activity, the purpose of this review is to present evidence on the possible role of HO-1 in these Central Nervous System (CNS) diseases. In addition, the possible therapeutic potential of targeting brain HO-1 is explored in this review.

Download Full-text

Potential for Treatment of Neurodegenerative Diseases with Natural Products or Synthetic Compounds that Stabilize Microtubules

Current Pharmaceutical Design ◽

10.2174/1381612826666200621171302 ◽

2020 ◽

Vol 26 (35) ◽

pp. 4362-4372

Author(s):

John H. Miller ◽

Viswanath Das

Keyword(s):

Natural Products ◽

Neurodegenerative Diseases ◽

In Vivo Models ◽

Synthetic Compounds ◽

Stabilizing Agents ◽

Animal Models Of Disease ◽

Model Studies ◽

Models Of Disease

No effective therapeutics to treat neurodegenerative diseases exist, despite significant attempts to find drugs that can reduce or rescue the debilitating symptoms of tauopathies such as Alzheimer’s disease, Parkinson’s disease, frontotemporal dementia, amyotrophic lateral sclerosis, or Pick’s disease. A number of in vitro and in vivo models exist for studying neurodegenerative diseases, including cell models employing induced-pluripotent stem cells, cerebral organoids, and animal models of disease. Recent research has focused on microtubulestabilizing agents, either natural products or synthetic compounds that can prevent the axonal destruction caused by tau protein pathologies. Although promising results have come from animal model studies using brainpenetrant natural product microtubule-stabilizing agents, such as paclitaxel analogs that can access the brain, epothilones B and D, and other synthetic compounds such as davunetide or the triazolopyrimidines, early clinical trials in humans have been disappointing. This review aims to summarize the research that has been carried out in this area and discuss the potential for the future development of an effective microtubule stabilizing drug to treat neurodegenerative disease.

Download Full-text