Current Pharmaceutical Design - Volume 26, Issue 7, 2020

This review presents the potential effects of dietary antioxidants on neurodegenerative diseases. The relationship between autoimmunity and antioxidants, and their preventive effect on neurodegenerative diseases are evaluated. The driven factors of neurodegeneration and the potential effects of natural antioxidants are summarized for Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, spongiform encephalopathy, Huntington’s disease, and amyotrophic lateral sclerosis. The effect of oxidative stress on neurodegenerative diseases and regulative effect of antioxidants on oxidative balance is discussed. This review provides beneficial information for the possible cure of neurodegenerative diseases with dietary intake of antioxidants.

Multiple sclerosis (MS) is an autoimmune demyelinating disorder with chronic inflammation in the central nervous system, manifested by both physical and cognitive disability. Neuroinflammation and neurodegeneration are the phenomena that appear in the central nervous system associated with various neurodegenerative disorders, including MS, Alzheimer’s diseases, amyotrophic lateral sclerosis and Parkinson’s disease. Prostaglandins are one of the major mediators of inflammation that exhibit an important function in enhancing neuroinflammatory and neurodegenerative processes. These mediators would help understand the pathophysiology of MS as the combination of antagonists or agonists of prostaglandins receptors could be beneficial during the treatment of MS. The present review focuses on the role played by different prostaglandins and the enzymes which produced them in the etiopathogenesis of MS.

Autism Spectrum Disorder (ASD) is an emerging health problem involving 1 out of every 68 children. The incidence rate of autism has increased 3 folds during the last 3 decades. Due to the illusive picture of aetiology, a considerable number of autistic children fail to receive proper behavioural and medicational treatment. The present study provides a cumulative account of autism risk factors. Several factors including the gene expression and gene mutations, environmental pollution, metal ion accumulation, exposure to pesticides, immune deficiencies, viral infections, mother’s age, health, mental status, mother’s interactions with the foetus, vaccination of mother and children, and modulations in gut microbiota have been debated. These risk factors may contribute to the development of autism either independently or synergistically leading to a broad spectrum of characteristics observed in autistic patients. The variable quantitative influence of a wide spectrum of risk factors may result in a unique set of features in each autistic individual. However, the exact mechanism behind the combined impact of various aetiological factors is poorly understood hindering the adaptation of specified and effective therapies.

Neurodegenerative diseases are a leading apprehension in underdeveloped and developed countries. The advancement of medical science is synonymous with an increase in life expectancy, which results in an aging population. Neurodegenerative diseases in the older population are on the rise globally. This review sums up the novel therapeutic approaches for Alzheimer’s and Parkinson's disease. Although most neurodegenerative diseases occur due to the accumulation of misfolded proteins, the mechanisms are not completely understood. Currently, only prophylactic therapies are available and none are preventive in nature. The World Health Organisation estimates that neurodegenerative diseases that cause cognitive and motor impairments will be the second most ubiquitous cause of death in the next decade, hence the need for novel therapeutic targets for these diseases is demanded. In Alzheimer’s, β-amyloid and tau proteinopathies are prevalent, whereas a prion-like increase of α- synuclein is the characteristic trait of Parkinson's disease.

Extracellular vesicles have an excellent ability to transfer their contents to cells. Extracellular vesicles can also be engineered to deliver therapeutic molecules to target cells. Although a number of studies have exploited synthesized nanoparticles in the treatment of neurological disease in the past few years, extracellular vesicles have been investigated and shown tremendous promise for clinical applications because they are safe and have strong targeting specificity. Different types of extracellular vesicles have been studied and modified for delivering therapeutic factors in neurological disease, including extracellular vesicles loaded with natural therapeutic factors and therapeutic molecules. In this review, we discuss delivery systems using extracellular vesicles containing molecules of interest and then focus on main strategies used for EV loading and surface modification. Discussing these important issues will support and facilitate the design and development of promising techniques and products for neurological therapy.

Background: Naturally-occurring products derived from living organisms have been shown to modulate various pharmacological and biological activities. Natural products protect against various diseases, which could be used for therapeutic assistance. Autophagy, a lysosome-mediated self-digestion pathway, has been implicated in a range of pathophysiological conditions and has recently gained attention for its role in several neurodegenerative diseases. Methods: In this current review, we emphasized the recent progress made in our understanding of the molecular mechanism of autophagy in different cellular and mouse models using naturally-occurring autophagy modulators for the management of several neurodegenerative diseases. Results: Accumulating evidence has revealed that a wide variety of natural compounds such as alkaloids, polyphenols, terpenoids, xanthonoids, flavonoids, lignans, disaccharides, glycolipoproteins, and saponins are involved in the modulation of the autophagy signaling pathway. These natural products have been used to treat various neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Amyotrophic lateral sclerosis, spinocerebellar ataxia, neuroblastoma, and glioblastoma. Although a number of synthetic autophagy regulators have been recognized as encouraging neurodegenerative therapeutic candidates, natural autophagy- regulating compounds have been of further interest as potential disease therapeutics, as they cause insignificant side effects. Conclusion: Existing in vitro and in vivo data are promising and highlight that naturally-occurring autophagyregulating compounds play an important role in the prevention and treatment of neurodegenerative disorders.

Introduction: The accumulation of amyloid-β peptide (Aβ) decreases cerebral blood flow in elderly people with Alzheimer’s disease (AD) and is believed to be the initiator of this disorder. As a traditional Chinese medicine, Yangxue Qingnao (YXQN) improves cerebral insufficiency and attenuates cognitive impairment, showing potential against AD. But whether YXQN has the ability to block Aβ self-aggregation is rarely reported. Objective: Here, we investigate the effects of YXQN on Aβ accumulation and its mediated cytotoxicity using a range of biochemical, biophysical, and cell-based approaches. Methods: Thioflavin T assay, transmission electron microscope, and 1H NMR experiments were used to investigate the effects of YXQN on Aβ fibrogenesis and aggregation. Far-UV CD spectra were acquired to assess the alteration of YXQN on the conformation of the amyloid protein. Three short Aβ42 peptides (AA 1-16, AA 17-33 and AA 28-42) were designed to analyse the Aβ42 epitope to which YXQN components bind. The effect of YXQN on Aβ-induced cytotoxicity was investigated through SH-SY5Y cell viability assay. Results: We provide evidence showing that YXQN clearly reduces Aβ42 fibrillogenesis and alters its β-sheet conformation, indicating the inhibition of primary nucleation of amyloid protein. Using the different Aβ short peptides, residues 17-33 were identified as the target epitope for YXNQ components interacting with Aβ42. Furthermore, in the SH-SY5Y cell injury model, our data show that high-dose YXQN attenuates amyloid-induced cytotoxicity approximately 60% and effectively ameliorates cell distortion in morphology. Conclusion: Based on these results, YXQN exerts a neuroprotective effect by inhibiting Aβ42 toxic aggregation, which has the potential to combat AD.

Keeping in view the public health-related issues of Alzheimer's disease (AD), its unpredictable occurrence and progression indicate the needs for best treatment options. The present bioinformatics study explores the binding pattern and molecular interactions between human acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) enzymes with natural compounds from Bacopa monnieri. The docking analysis between natural compounds as a ligand and AChE, BuChE as a receptor was completed using MGL tools Autodock 4.2 module. The analysis of the hydrophobic interactions, inhibition constants, and hydrogen bonds may indicates that they play a significant role in finding out the interacting position at the active site. However, after analyzing the binding energy (ΔG), the documented data shows that bacoside X, bacoside A, 3-beta-D-glucosylstigmasterol and daucosterol could be good inhibitors in the inhibition of AChE and BuChE activities. Therefore, our study indicates that the inhibition constants of the aforesaid natural compounds of Bacopa can be utilized for the development of inhibitors.