-
1.
Repurposing of Copper(II)-chelating Drugs for the Treatment of Neurodegenerative Diseases.
Lanza, V, Milardi, D, Di Natale, G, Pappalardo, G
Current medicinal chemistry. 2018;(4):525-539
Abstract
BACKGROUND There is mounting urgency to find new drugs for the treatment of neurodegenerative disorders. A large number of reviews have exhaustively described either the molecular or clinical aspects of neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's (PD). Conversely, reports outlining how known drugs in use for other diseases can also be effective as therapeutic agents in neurodegenerative diseases are less reported. This review focuses on the current uses of some copper(II) chelating molecules as potential drug candidates in neurodegeneration. METHODS Starting from the well-known harmful relationships existing between the dyshomeostasis and mis-management of metals and AD onset, we surveyed the experimental work reported in the literature, which deals with the repositioning of metal-chelating drugs in the field of neurodegenerative diseases. The reviewed papers were retrieved from common literature and their selection was limited to those describing the biomolecular aspects associated with neuroprotection. In particular, we emphasized the copper(II) coordination abilities of the selected drugs. RESULTS Copper, together with zinc and iron, are known to play a key role in regulating neuronal functions. Changes in copper homeostasis are crucial for several neurodegenerative disorders. The studies included in this review may provide an overview on the current strategies aimed at repurposing copper (II) chelating drugs for the treatment of neurodegenerative disorders. Starting from the exemplary case of clioquinol repurposing, we discuss the challenge and the opportunities that repurposing of other metal-chelating drugs may provide (e.g. PBT-2, metformin and cyclodipeptides) in the treatment of neurodegenerative disease. CONCLUSIONS In order to improve the success rate of drug repositioning, comprehensive studies on the molecular mechanism and therapeutic efficacy are still required. The present review upholds that drug repurposing makes significant advantages over drug discovery since repositioned drugs had already passed the safety and toxicity tests. Promising drug candidates in neurodegenerative diseases may be represented by copper chelating classes of drugs, provided that sufficient details on their mechanism of action are available to encourage further investigations and clinical trials.
-
2.
Protective Effect of Glucosinolates Hydrolytic Products in Neurodegenerative Diseases (NDDs).
Jaafaru, MS, Abd Karim, NA, Enas, ME, Rollin, P, Mazzon, E, Abdull Razis, AF
Nutrients. 2018;(5)
Abstract
Crucifer vegetables, Brassicaceae and other species of the order Brassicales, e.g., Moringaceae that are commonly consumed as spice and food, have been reported to have potential benefits for the treatment and prevention of several health disorders. Though epidemiologically inconclusive, investigations have shown that consumption of those vegetables may result in reducing and preventing the risks associated with neurodegenerative disease development and may also exert other biological protections in humans. The neuroprotective effects of these vegetables have been ascribed to their secondary metabolites, glucosinolates (GLs), and their related hydrolytic products, isothiocyanates (ITCs) that are largely investigated for their various medicinal effects. Extensive pre-clinical studies have revealed more than a few molecular mechanisms of action elucidating multiple biological effects of GLs hydrolytic products. This review summarizes the most significant and up-to-date in vitro and in vivo neuroprotective actions of sulforaphane (SFN), moringin (MG), phenethyl isothiocyanate (PEITC), 6-(methylsulfinyl) hexyl isothiocyanate (6-MSITC) and erucin (ER) in neurodegenerative diseases.
-
3.
Flavonoids in the Treatment of Alzheimer's and Other Neurodegenerative Diseases.
Airoldi, C, La Ferla, B, D Orazio, G, Ciaramelli, C, Palmioli, A
Current medicinal chemistry. 2018;(27):3228-3246
Abstract
Flavonoids are phytochemicals present in almost all terrestrial plants and, as a consequence, in plant-based foods, and thus consumed by humans through diet. Recent evidences suggest that several flavonoids have positive effects against dementia and Alzheimer's disease, reversing age-related declines in neurocognitive performances. In this review, we provide a general classification of natural and synthetic flavonoids, a description of their physico-chemical properties, in particular their redox properties and stability, and an extensive overview about their biological activities and structure-activity relationship in the field of neurodegenerative diseases. In addition, a section will be dedicated to the synthetic strategies for the preparation of bioactive derivatives. This information will be essential for the design and development of new drugs that can improve brain functions.
-
4.
Herbal and Holistic Solutions for Neurodegenerative and Depressive Disorders: Leads from Ayurveda.
Sharma, R, Kabra, A, Rao, MM, Prajapati, PK
Current pharmaceutical design. 2018;(22):2597-2608
Abstract
Neuropsychiatric and neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, schizophrenia, epilepsy, depression and anxiety pose a sizable global health problem, accompanying substantial burden of disorders, suicides, physical comorbidities, high fiscal expenses, and poor quality of life. There is a recent upsurge in global interest toward the area of traditional therapies and phytomedicines are widely admired by researchers owing to their natural source and fewer side effects. On the contrary, conventional synthetic drugs have been reported with undesirable but inevitable ill effects having poor patient compliance. Thus, herbal medicines are being preferred over synthetic drug therapies as an effective remedy for many brain disorders. Ayurveda provides a holistic approach to treatment along with several nootropic herbs having multi-dimensional bioactivities in various disorders. Scattered information is available pertaining to traditional Ayurvedic remedial options for various mental disorders. Present review encompasses: (i) common brain disorders and the associated changes (ii) Ayurvedic holistic approach to manage neurodegenerative and depressive disorders, and (iii) important Ayurvedic single herbs and polyherbal formulations with description of their traditional usage and administration. Concomitantly, it opens up for future investigations and standardization on Ayurvedic nootropic herbs.
-
5.
Role of Plant Derived Alkaloids and Their Mechanism in Neurodegenerative Disorders.
Hussain, G, Rasul, A, Anwar, H, Aziz, N, Razzaq, A, Wei, W, Ali, M, Li, J, Li, X
International journal of biological sciences. 2018;(3):341-357
Abstract
Neurodegenerative diseases are conventionally demarcated as disorders with selective loss of neurons. Conventional as well as newer molecules have been tested but they offer just symptomatic advantages along with abundant side effects. The discovery of more compelling molecules that can halt the pathology of these diseases will be considered as a miracle of present time. Several synthetic compounds are available but they may cause several other health issues. Therefore, natural molecules from the plants and other sources are being discovered to replace available medicines. In conventional medicational therapies, several plants have been reported to bestow remedial effects. Phytochemicals from medicinal plants can provide a better and safer alternative to synthetic molecules. Many phytochemicals have been identified that cure the human body from a number of diseases. The present article reviews the potential efficacy of plant-derived alkaloids, which possess potential therapeutic effects against several NDDs including Alzheimer's disease (AD), Huntington disease (HD), Parkinson's disease (PD), Epilepsy, Schizophrenia, and stroke. Alkaloids include isoquinoline, indole, pyrroloindole, oxindole, piperidine, pyridine, aporphine, vinca, β-carboline, methylxanthene, lycopodium, and erythrine byproducts. Alkaloids constitute positive roles in ameliorating pathophysiology of these illnesses by functioning as muscarinic and adenosine receptors agonists, anti-oxidant, anti-amyloid and MAO inhibitors, acetylcholinestrase and butyrylcholinesterase inhibitor, inhibitor of α-synuclein aggregation, dopaminergic and nicotine agonist, and NMDA antagonist.
-
6.
Modifying progression of aging and reducing the risk of neurodegenerative diseases by probiotics and synbiotics.
Lye, HS, Lee, YT, Ooi, SY, Teh, LK, Lim, LN, Wei, LK
Frontiers in bioscience (Elite edition). 2018;(2):344-351
Abstract
Aging, which affects most of the multi-cellular organisms, is due to a potentially complex set of mechanisms that collectively cause a time-dependent decline of physiological functions. Aging restrains longevity and leads to neurodegenerative diseases including dementia, Alzheimer's disease and lacunar stroke. Human microbiota is now considered to have a strong impact on the progression of aging. The impact of aging and the risk of neurodegenerative diseases can be reduced by using probiotics, or preferably by combining probiotics and prebiotics, also known as synbiotics, that can drastically modify the composition of gut microbiome.
-
7.
Herbal Medicines in Neurodegenerative Disorders: An Evolutionary Approach through Novel Drug Delivery System.
Dubey, SK, Singhvi, G, Krishna, KV, Agnihotri, T, Saha, RN, Gupta, G
Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer. 2018;(3):199-208
Abstract
Neurodegenerative disorders are one of the most debilitating, chronic, and often irreversible disorders of the brain and have gained a widespread attention of researchers. Since current therapeutics seem to be inadequate treatment of these disorders, scientists are exploring their options with herbal drugs. This review discusses herbal constituents with the potential to treat neurological disorders. These herbal drugs, when combined with a novel delivery system, provide added advantages to nanocarrier systems. The review also presents research on different herbals through liposomes, polymeric nanoparticles, and solid lipid nanoparticles. The data are collected from various online databases, including PubMed, ScienceDirect, references from relevant review articles, and other official publications. Broad search term criteria are followed for searches so that all pertinent information is included.
-
8.
Genetic and clinical aspects of Wolfram syndrome 1, a severe neurodegenerative disease.
Rigoli, L, Bramanti, P, Di Bella, C, De Luca, F
Pediatric research. 2018;(5):921-929
Abstract
Wolfram syndrome 1 (WS1) is a rare autosomal recessive neurodegenerative disease characterized by diabetes insipidus, diabetes mellitus, optic atrophy, deafness, and other abnormalities. WS1 usually results in death before the age of 50 years. The pathogenesis of WS1 is ascribed to mutations of human WFS1 gene on chromosome 4p encoding a transmembrane protein called wolframin, which has physiological functions in membrane trafficking, secretion, processing, and/or regulation of ER calcium homeostasis. Different types of WFS1 mutations have been identified, and some of these have been associated with a dominant, severe type of WS. Mutations of CISD2 gene cause autosomal recessive Wolfram syndrome 2 (WS2) characterized by the absence of diabetes insipidus and psychiatric disorders, and by bleeding upper intestinal ulcer and defective platelet aggregation. Other WFS1-related disorders such as DFNA6/14/38 nonsyndromic low-frequency sensorineural hearing loss and Wolfram syndrome-like disease with autosomal dominant transmission have been described. WS1 is a devastating disease for the patients and their families. Thus, early diagnosis is imperative to enable proper prognostication, prevent complications, and reduce the transmission to further progeny. Although there is currently no effective therapy, potential new drugs have been introduced, attempting to improve the progression of this fatal disease.
-
9.
ApoE and Neurodegenerative Diseases in Aging.
Yin, Y, Wang, Z
Advances in experimental medicine and biology. 2018;:77-92
Abstract
Age and apolipoprotein E (ApoE) are the mightiest risk factors for dementia and cardiovascular diseases, but the underlying mechanisms remain unclear. In human, ApoE has three isoforms, ApoE2, ApoE3, and ApoE4, which are expressed by the polymorphic alleles: ɛ2, ɛ3, and ɛ4. Among the three polymorphic alleles, apoE ε4 is the most risk gene. ApoE is the main ligand for the low-density lipoprotein (LDL) receptor and the LDL receptor-related protein (LRP), functioning as the component of plasma lipoproteins in the transportation of lipids. Physiologically, ApoE is a multifunctional protein with central roles in lipid metabolism; it transports lipids, including cholesterol, through the cerebrospinal fluid (CSF) and plasma. ApoE expression regulation and apoE gene polymorphism have an important connection with neurological or neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), ischemic stroke, and other diseases.
-
10.
Glaucoma and the brain: Trans-synaptic degeneration, structural change, and implications for neuroprotection.
Lawlor, M, Danesh-Meyer, H, Levin, LA, Davagnanam, I, De Vita, E, Plant, GT
Survey of ophthalmology. 2018;(3):296-306
Abstract
A recent hypothesis to enter the literature suggests that glaucoma is a neurodegenerative disease. The basis for this has been the finding of central nervous system changes in glaucoma patients on histology and neuroimaging. It is known that retinal ganglion cell pathology of any cause leads to anterograde and retrograde retinal ganglion cell degeneration, as well as trans-synaptic (transneuronal) anterograde degeneration. Trans-synaptic degeneration has been demonstrated in a range of optic neuropathies including optic nerve transection, optic neuritis, and hereditary optic neuropathies. More recently, similar changes have been confirmed in glaucoma patients using the neuroimaging techniques of voxel-based morphometry and diffusion tensor imaging. Some studies have reported brain changes in glaucoma outside the retino-geniculo-cortical pathway; however, these are preliminary and exploratory in nature. Further research is required to identify whether the degenerative brain changes in glaucoma are entirely secondary to the optic neuropathy or whether there is additional primary central nervous system pathology. This has critical implications for neuroprotective and regenerative treatment strategies and our basic understanding of glaucoma.