Natural Products-Based Drugs: Potential Therapeutics against Alzheimer's Disease and other Neurological Disorders

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Background

Alzheimer’s disease (AD) is the most common neurodegenerative disorder, characterized by memory impairment, behavioral turbulence, cognitive dysfunction and imperfection in routine life activities. AD is the most common cause of dementia among people aged 65 years and older, with about 35 million sufferers worldwide. It is the fifth leading cause of death in people above 65 years of age and is predicted to affect 1 in 85 people globally by 2050. The most important pathological aspects of AD include the deficiency of the neurotransmitter acetylcholine, deposition of amyloid plaques (Aβ), neurofibrillary tangles (NFT), oxidative stress, and glutamatergic system abnormalities. It is the most common cause of dementia and has a devastating impact on public health and society. AD is a multi-factorial disease with an extremely complex pathogenesis that includes both genetic and environmental factors.

Among clinically approved drugs, four are cholinesterase inhibitors including tacrine, donepezil, rivastigmine, and galantamine, whereas the fifth one is a glutamatergic system modifier -memantine. No drug is clinically approved for the management of Aβ and NFTs, yet several are currently in clinical trials. Natural products play a significant role in the drug discovery and development process. The main advantage of natural products as a source of lead compounds drugs are tied to serious side effects like hepatotoxicity, and are only useful in mild types of AD. Therefore, it is necessary to search for new, safe, and effective drug candidates. Natural products are potential sources of novel bioactive compounds and have had an extensive history of therapeutic utility. Galantamine, an anticholinestrase alkaloid was isolated from the snowdrop, and is approved for the therapy of AD. Research has been directed at studying the biological effects of traditionally used plants.

This Research Topic aims to update our understanding of the current drug development for the management of Alzheimer disease and dementia and contribute to a critical assessment of the state of the art. It will include detailed studies on phytochemically well-defined extracts, and isolated pure compounds from plants and fungi against various targets of Alzheimer's disease as exemplified in the following themes. Mechanistic studies on the modulation of oxidative stress in relevant in vitro / in vivo models (see below), inhibition of cholinesterases and anti-amyloid and glutametergic system modulating effects are welcome. [including on BACE1 (beta-secretase) enzyme inhibition and effect on these compounds on amyloid load (Neuritic plaques) in transgenic animals]. Genetic studies related to Alzheimer's disease, disease markers, BDNF, immuno-histochemistry studies are welcomed. Clinical studies will only be considered if they are well-designed and fully comply with the requirements of conducting and reporting such studies Furthermore, reviews of natural products based drug development with a broader focus also including other neurological disorders like depression, anxiety, convulsions will be welcomed for this Research Topic if they provide a critical and specific appraisal of the current state of the art in one aspect of the topic and offer new perspectives on it. This may include regional uses of plants and fungi (if there is sufficient evidence that there is a link between traditional uses and the bioscientific studies) or studies focusing on specific targets relevant to Alzheimer’s disease.

The following basic guidelines, focused on best practice in ethnopharmacology, should be followed by all submissions:`

General
- Positive and negative controls must be included.
- Models must be pharmacologically relevant and plausible - a complex question depending on the specific goals of the study. Authors must consider the ethical acceptability of further in vivo studies on an already well-studied species, demonstrating some common activity (e.g. an anti-inflammatory effect studied in the rat-paw oedema)

Chemical
-Composition of the study material - The composition of the study material must be described adequate-ly. Manuscripts relating to crude plant extracts, where an individual active agent or a detailed phytochemical characteriza-tion of all extracts is not clearly identified and quantified are not acceptable.
-Composition of the study material - Where ‘pure’ compounds are used the level of purity must be reported.
- Dose ranges must be pharmacologically relevant. While impossible to define an exact cut-off, studies testing extracts at implausibly high doses are increasingly common in the literature.
-Antioxidant activity - Simple in silico and pharmacologically irrelevant assays for antioxidant activity (e.g. the DPPH as-say, FRAP (Ferric Reducing Ability of Plasma), ABTS (2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)) are not acceptable as a main tool for assessing an extract or a compound for activity. In case of AD, there is no evidence that, for example, in silico studies, provide any evidence relevant for the condition.

Botanical
- The identification of the study material needs to be defined well. All species must be fully validated using www.theplantlist.org or http://mpns.kew.org/mpns-portal/.

Keywords: Alzheimer Disease, Dementia, Natural Products, Neuropathies, Anxiety, Depression, Convulsions, Cognition, Cholinesterase inhibitors, Amyloid plaques (Aβ), Neurofibrillary tangles (NFTs), Alzheimer's disease genetics, Oxidative stress

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