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Preclinical and clinical issues in Alzheimer's disease drug research and development

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194339 Year: Pages: 100 DOI: 10.3389/978-2-88919-433-9 Language: English
Publisher: Frontiers Media SA
Subject: Therapeutics --- Science (General)
Added to DOAB on : 2016-01-19 14:05:46
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Abstract

Alzheimer’s disease (AD) is a chronic neurodegenerative disorder characterized by progressive cognitive dysfunction and memory loss, inability to perform the activities of daily living and mood disorders. According to the so-called “amyloid cascade hypothesis”, amyloid-ß- peptide (Aß), produced by beta- and gamma- secretase-mediated cleavages of the amyloid precursor protein (APP), plays a pivotal role in the pathogenesis of AD. Aß was also shown to contribute to AD pathology by stimulating the hyperphosphorylation of tau which is responsible for the formation of neurofibrillary tangles. However, the “amyloid cascade hypothesis” was challenged by other theories which lend support to the idea that Aß is not causative but can be considered as an “innocent bystander” in AD. Although preclinical research generated impressive lines of evidence about the several intracellular mechanism(s) whose impairment leads to the onset and progression of AD, clinical research aimed at the development of new drugs capable of preventing or delaying the onset of neuronal damage in AD patients has produced limited results. The drugs currently available for the treatment of AD are acetylcholinesterase inhibitors (AChEI) and the NMDA glutamate receptor antagonist memantine. The AChEI increase acetylcholine levels in the synaptic cleft, which are reduced because of the progressive damage of cholinergic neurons in cognitive brain areas (e.g. amygdala, hippocampus, and frontal cortex), whereas memantine is used to prevent/reduce calcium-dependent excitotoxic neuronal cell death. Both classes of drugs have been shown to improve symptoms related to cognitive decline, but their effects are confined largely to patients with mild to moderate AD, in particular during the first year or so of treatment. An alternative to this symptomatic treatments involves the use of drugs that intervene in the pathogenesis of the disease. Recently, monoclonal antibodies against Aß were proposed as novel agents capable to remove Aß from the brain thus preventing neuronal damage. The research topic focuses on the preclinical and clinical evidence about the several factors that contribute to the pathogenesis of AD as well as the potential therapeutic role of new classes of drugs still under preclinical or clinical development.

Plant Natural Products for Human Health

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ISBN: 9783038977124 Year: Pages: 514 DOI: 10.3390/books978-3-03897-713-1 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Therapeutics --- Medicine (General)
Added to DOAB on : 2019-04-05 10:34:31
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Abstract

Plants have served mankind as an important source of foods and medicines. While we all consume plants and their products for nutritional support, a majority of the world population also rely on botanical remedies to meet their health needs, either as their own “traditional medicine” or as “complementary and alternative medicine”. From a pharmaceutical point of view, many compounds obtained from plant sources have long been known to possess bio/pharmacological activities, and historically, plants have yielded many important drugs for human use, from morphine discovered in the early nineteenth century to the more recent paclitaxel and artemisinin. Today, we are witnessing a global resurgence in interest and use of plant-based therapies and botanical products, and natural products remain an important and viable source of lead compounds in many drug discovery programs.This Special Issue on “Plant Natural Products for Human Health” compiles a series of scientific reports to demonstrate the medicinal potentials of plant natural products. It covers a range of disease targets, such as diabetes, inflammation, cancer, neurological disease, cardiovascular disease, liver damage, bacterial, and fungus infection and malarial. These papers provide important insights into the current state of research on drug discovery and new techniques. It is hoped that this Special Issue will serve as a timely reference for researchers and scholars who are interested in the discovery of potentially useful molecules from plant sources for health-related applications.

Keywords

heat-process --- onion --- calorie restriction --- Amadori rearrangement compounds --- hyperglycemia --- A549 cells --- hinokitiol --- MMPs --- p53/Bax --- antioxidant enzymes --- caspases --- migration --- cannabinoid type 1 receptor --- endoplasmic reticulum stress --- gluconeogenesis --- gomisin N --- lipogenesis --- insulin resistance --- garlic --- ischemia --- heme oxygenase --- reperfusion --- heart --- Keap1 --- Nrf2 --- Neuroprotective --- PC12 cells --- PhGs --- anti-malaria activity --- plants --- natural products --- ethnopharmacology --- Plasmodium parasites --- copaiba --- oleoresin --- essential oil --- sesquiterpenoids --- diterpenoids --- biological activity --- molecular targets --- Astragali Radix --- astragaloside IV --- genistein --- mitochondrial bioenergetics --- oxygen consumption rate --- natural products --- drug design and development --- innovation --- automation --- computational softwares --- bioinformatics --- precision medicine --- omics --- global health --- sweet orange --- bitter orange --- neroli --- orange petitgrain --- mandarin --- lemon --- lime --- grapefruit --- bergamot --- yuzu --- kumquat --- cannabigerol --- Cannabis sativa --- neuroinflammation --- oxidative stress --- phytocannabinoid --- iridoids --- nuclear factor-kappaB --- mitogen-activated protein kinase --- anti-inflammation --- Ziziphus jujuba --- triterpenic acids --- pharmacokinetic study --- acute liver injury --- A? --- AD --- lychee seed --- neuroinflammation --- catechin --- procyanidin A2 --- apoptosis --- cinnamamides --- antistaphylococcal activity --- time-kill assay --- biofilm --- antitubercular activity --- MTT assay --- antifungal activity --- PET inhibition --- toxicity --- structure–activity relationship --- bleeding time --- flavonoid --- morin hydrate --- OH· free radical --- platelet activation --- protein kinase --- thromboembolism --- Glycyrrhiza uralensis --- prenylated flavonoids --- antiproliferation --- differentiation --- melanoma cell --- adjuvant-induced arthritis --- arthritis --- celastrol --- curcumin --- dietary supplements --- EGCG --- green tea --- inflammation --- liposomes --- microbiome --- nanoparticles --- natural products --- resveratrol --- rheumatoid arthritis --- targeted delivery --- traditional medicine --- Tripterygium wilfordii --- triptolide --- Penthorum chinense Pursh --- NAFLD --- hepatic steatosis --- flavonoids --- SIRT1 --- AMPK --- dihydromyricetin --- myocardial hypertrophy --- oxidative stress --- sirtuin 3 --- ginseng --- human-hair-follicle dermal papilla cells --- WNT/?-catenin --- Shh/Gli --- TGF-? --- BMP/Smad --- mouse-hair growth --- Panax notoginseng saponins --- aspirin --- HepaRG cells --- herb–drug interactions --- P. eryngii --- glucans --- inflammation --- inflammatory bowel disease --- medicinal plants --- phytochemicals --- scoulerine --- bergapten --- immunomodulator --- adjuvant --- cytoxicity --- dendritic cells --- immune modulation --- APAP --- acetaminophen --- hepatotoxicity --- hpatoprotection --- paracetamol --- animals --- preclinical studies --- natural products --- small molecules --- phytochemicals --- plants --- fucoidan --- acetaminophen --- Nrf2 --- oxidative stress --- hepatotoxicity --- plant natural product --- drug discovery --- human health

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