Abstract
The incidence of neurodegenerative diseases, such as Alzheimer’s disease (AD), increases continuously demanding the urgent development of anti-Alzheimer’s agents. Marine organisms (MO) have to create their own defenses due to the adverse environment where they live and so synthesize several classes of compounds, such as akaloids, to defend themselves. Therefore, the identification of marine natural products with neuroprotective effects is a necessity. Being that AD is not only a genetic but also an environmental complex disease, a treatment for AD remains to discover. As the major clinical indications (CI) of AD are extracellular plaques formed by β-amyloid (Aβ) protein, intracellular neurofibrillary tangles (NFTs) formed by hyper phosphorylated τ-protein, uncommon inflammatory response and neuron apoptosis and death caused by oxidative stress, alkaloids that may decrease CI, might be used against AD. Most of the alkalolids with those properties are derivatives of the amino acid tryptophan mainly with a planar indole scaffold. Certainly, alkaloids targeting more than one CI, multitarget-directed ligands (MTDL), have the potential to become a lead in AD treatment. Alkaloids to have a maximum of activity against CI, should be planar and contain halogens and amine quaternization.
Highlights
Today about 50 million persons are having dementia and it is foreseen that this number will increase 60% in 2030 and to 180% in 2050 [1]
The development of early onset of AD (EOAD) is associated with genetic mutations, genes such as amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) which are involved in the production of the β-amyloid (Aβ) peptides
8-hydroxymanzamine A (17), showed a strong ability to inhibit tau phosphorylation within cells. From these data it can be concluded that the activity of GSK3β of the manzamine alkaloids is reduced by the hydrogenation of the double bond at C-32/C-33 and oxidation of C-31 to the ketone
Summary
Today about 50 million persons are having dementia and it is foreseen that this number will increase 60% in 2030 and to 180% in 2050 [1]. As MTs may be formed by different isoforms of tubulin they have a dynamic nature and interact with associated proteins (MAPs), being very important in determining the morphology, stability, and their function in different cell types [19]. The stabilization of MTs may potentially prevent AD progression Another way to prevent the disease is reducing hyper-phosphorylation of τ-protein, and, so, avoid MTs dysfunction. Nicotinic ACh receptors (nAChRs) in the central nervous system, control the liberation of other neurotransmitters and are involved in cognitive processes and memory [47,48] Another strategy to combat AD is controlling nAChRs. So, the disease pathology can progress through different pathways which can even be related. (Section 2.5). hAChE—human recombinant acetylcholinesterase; NA—not active; NE—not evaluated
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