17
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Iridoids and Other Monoterpenes in the Alzheimer’s Brain: Recent Development and Future Prospects

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Iridoids are a class of monoterpenoid compounds constructed from 10-carbon skeleton of isoprene building units. These compounds in their aglycones and glycosylated forms exist in nature to contribute to mechanisms related to plant defenses and diverse plant-animal interactions. Recent studies have also shown that iridoids and other structurally related monoterpenes display a vast array of pharmacological effects that make them potential modulators of the Alzheimer’s disease (AD). This review critically evaluates the therapeutic potential of these natural products by assessing key in vitro and in vivo data published in the scientific literature. Mechanistic approach of scrutiny addressing their effects in the Alzheimer’s brain including the τ-protein phosphorylation signaling, amyloid beta (Aβ) formation, aggregation, toxicity and clearance along with various effects from antioxidant to antiinflammatory mechanisms are discussed. The drug likeness of these compounds and future prospects to consider in their development as potential leads are addressed.

          Related collections

          Most cited references165

          • Record: found
          • Abstract: found
          • Article: not found

          p38 MAP-kinases pathway regulation, function and role in human diseases.

          Mammalian p38 mitogen-activated protein kinases (MAPKs) are activated by a wide range of cellular stresses as well as in response to inflammatory cytokines. There are four members of the p38MAPK family (p38alpha, p38beta, p38gamma and p38delta) which are about 60% identical in their amino acid sequence but differ in their expression patterns, substrate specificities and sensitivities to chemical inhibitors such as SB203580. A large body of evidences indicates that p38MAPK activity is critical for normal immune and inflammatory response. The p38MAPK pathway is a key regulator of pro-inflammatory cytokines biosynthesis at the transcriptional and translational levels, which makes different components of this pathway potential targets for the treatment of autoimmune and inflammatory diseases. However, recent studies have shed light on the broad effect of p38MAPK activation in the control of many other aspects of the physiology of the cell, such as control of cell cycle or cytoskeleton remodelling. Here we focus on these emergent roles of p38MAPKs and their implication in different pathologies.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Compromised MAPK signaling in human diseases: an update.

            The mitogen-activated protein kinases (MAPKs) in mammals include c-Jun NH2-terminal kinase (JNK), p38 MAPK, and extracellular signal-regulated kinase (ERK). These enzymes are serine-threonine protein kinases that regulate various cellular activities including proliferation, differentiation, apoptosis or survival, inflammation, and innate immunity. The compromised MAPK signaling pathways contribute to the pathology of diverse human diseases including cancer and neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. The JNK and p38 MAPK signaling pathways are activated by various types of cellular stress such as oxidative, genotoxic, and osmotic stress as well as by proinflammatory cytokines such as tumor necrosis factor-α and interleukin 1β. The Ras-Raf-MEK-ERK signaling pathway plays a key role in cancer development through the stimulation of cell proliferation and metastasis. The p38 MAPK pathway contributes to neuroinflammation mediated by glial cells including microglia and astrocytes, and it has also been associated with anticancer drug resistance in colon and liver cancer. We here summarize recent research on the roles of MAPK signaling pathways in human diseases, with a focus on cancer and neurodegenerative conditions.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Mechanisms of Aβ Clearance and Degradation by Glial Cells

              Glial cells have a variety of functions in the brain, ranging from immune defense against external and endogenous hazardous stimuli, regulation of synaptic formation, calcium homeostasis, and metabolic support for neurons. Their dysregulation can contribute to the development of neurodegenerative disorders, including Alzheimer’s disease (AD). One of the most important functions of glial cells in AD is the regulation of Amyloid-β (Aβ) levels in the brain. Microglia and astrocytes have been reported to play a central role as moderators of Aβ clearance and degradation. The mechanisms of Aβ degradation by glial cells include the production of proteases, including neprilysin, the insulin degrading enzyme, and the endothelin-converting enzymes, able to hydrolyse Aβ at different cleavage sites. Besides these enzymes, other proteases have been described to have some role in Aβ elimination, such as plasminogen activators, angiotensin-converting enzyme, and matrix metalloproteinases. Other relevant mediators that are released by glial cells are extracellular chaperones, involved in the clearance of Aβ alone or in association with receptors/transporters that facilitate their exit to the blood circulation. These include apolipoproteins, α2macroglobulin, and α1-antichymotrypsin. Finally, astrocytes and microglia have an essential role in phagocytosing Aβ, in many cases via a number of receptors that are expressed on their surface. In this review, we examine all of these mechanisms, providing an update on the latest research in this field.
                Bookmark

                Author and article information

                Journal
                Molecules
                Molecules
                molecules
                Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry
                MDPI
                1420-3049
                07 January 2018
                January 2018
                : 23
                : 1
                : 117
                Affiliations
                Pharmacognosy Research Laboratories & Herbal Analysis Services, University of Greenwich, Central Avenue, Chatham-Maritime, Kent ME4 4TB, UK; s.habtemariam@ 123456herbalanalysis.co.uk ; Tel.: +44-208-331-8302/8424
                Article
                molecules-23-00117
                10.3390/molecules23010117
                6017424
                29316661
                bf862dc2-9328-4ef5-8147-afb19761c221
                © 2018 by the author.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 26 December 2017
                : 05 January 2018
                Categories
                Review

                monoterpenes,iridoids,alzheimer’s disease,amyloid beta,drug likeness,multiple mechanisms

                Comments

                Comment on this article