18
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Cholinesterase inhibitors as Alzheimer's therapeutics

      review-article
      Molecular Medicine Reports
      D.A. Spandidos
      Alzheimer's, dementia, cholinesterase, inhibitor, multi-target

      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

          Alzheimer's disease (AD) is one of the most common forms of dementia. AD is a chronic syndrome of the central nervous system that causes a decline in cognitive function and language ability. Cholinergic deficiency is associated with AD, and various cholinesterase inhibitors have been developed for the treatment of AD, including naturally-derived inhibitors, synthetic analogues and hybrids. Currently, the available drugs for AD are predominantly cholinesterase inhibitors. However, the efficacy of these drugs is limited as they may cause adverse side effects and are not able to completely arrest the progression of the disease. Since AD is multifactorial disease, dual and multi-target inhibitors have been developed. The clinical applications and the limitations of the inhibitors used to treat AD are discussed in the present review. Additionally, this review presents the current status and future directions for the development of novel drugs with reduced toxicity and preserved pharmacological activity.

          Related collections

          Most cited references85

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

          The cholinergic hypothesis of geriatric memory dysfunction.

          Biochemical, electrophysiological, and pharmacological evidence supporting a role for cholinergic dysfunction in age-related memory disturbances is critically reviewed. An attempt has been made to identify pseudoissues, resolve certain controversies, and clarify misconceptions that have occurred in the literature. Significant cholinergic dysfunctions occur in the aged and demented central nervous system, relationships between these changes and loss of memory exist, similar memory deficits can be artificially induced by blocking cholinergic mechanisms in young subjects, and under certain tightly controlled conditions reliable memory improvements in aged subjects can be achieved after cholinergic stimulation. Conventional attempts to reduce memory impairments in clinical trials hav not been therapeutically successful, however. Possible explanations for these disappointments are given and directions for future laboratory and clinical studies are suggested.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            A perspective on multi-target drug discovery and design for complex diseases

            Diseases of infection, of neurodegeneration (such as Alzheimer’s and Parkinson’s diseases), and of malignancy (cancers) have complex and varied causative factors. Modern drug discovery has the power to identify potential modulators for multiple targets from millions of compounds. Computational approaches allow the determination of the association of each compound with its target before chemical synthesis and biological testing is done. These approaches depend on the prior identification of clinically and biologically validated targets. This Perspective will focus on the molecular and computational approaches that underpin drug design by medicinal chemists to promote understanding and collaboration with clinical scientists.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              The Importance of Tau Phosphorylation for Neurodegenerative Diseases

              Fibrillar deposits of highly phosphorylated tau are a key pathological feature of several neurodegenerative tauopathies including Alzheimer’s disease (AD) and some frontotemporal dementias. Increasing evidence suggests that the presence of these end-stage neurofibrillary lesions do not cause neuronal loss, but rather that alterations to soluble tau proteins induce neurodegeneration. In particular, aberrant tau phosphorylation is acknowledged to be a key disease process, influencing tau structure, distribution, and function in neurons. Although typically described as a cytosolic protein that associates with microtubules and regulates axonal transport, several additional functions of tau have recently been demonstrated, including roles in DNA stabilization, and synaptic function. Most recently, studies examining the trans-synaptic spread of tau pathology in disease models have suggested a potential role for extracellular tau in cell signaling pathways intrinsic to neurodegeneration. Here we review the evidence showing that tau phosphorylation plays a key role in neurodegenerative tauopathies. We also comment on the tractability of altering phosphorylation-dependent tau functions for therapeutic intervention in AD and related disorders.
                Bookmark

                Author and article information

                Journal
                Mol Med Rep
                Mol Med Rep
                Molecular Medicine Reports
                D.A. Spandidos
                1791-2997
                1791-3004
                August 2019
                11 June 2019
                11 June 2019
                : 20
                : 2
                : 1479-1487
                Affiliations
                Department of Chemistry, Faculty of Physical Sciences, Shree Guru Gobind Singh Tricentenary University, Gurugram, Haryana 122505, India
                Author notes
                Correspondence to: Dr Kamlesh Sharma, Department of Chemistry, Faculty of Physical Sciences, Shree Guru Gobind Singh Tricentenary University, Gurgaon-Badli Road Chandu, Budhera, Gurugram, Haryana 122505, India, E-mail: drkamlesh_fps@ 123456sgtuniversity.org
                Article
                mmr-20-02-1479
                10.3892/mmr.2019.10374
                6625431
                31257471
                30a16fc9-4ccb-4c5f-85b8-ce835e3a8879
                Copyright: © Sharma et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 23 October 2018
                : 09 May 2019
                Categories
                Review

                alzheimer's,dementia,cholinesterase,inhibitor,multi-target
                alzheimer's, dementia, cholinesterase, inhibitor, multi-target

                Comments

                Comment on this article