Beneficial Effects of Lysosome-Modulating and Other Pharmacological and Nanocarrier Agents on Amyloid-beta-treated Cells

Marie      V. Kanazirska; Philipp      M. Fuchs; Liping      Chen; Sumit      Lal; Jyoti      Verma; Peter      M. Vassilev

doi:10.2174/138920112804724909

Abstract

The progression of Alzheimer’s disease (AD) is accompanied by disturbances of the endosome/lysosome (EL) system and there is accumulation of peptides of the AD-associated amyloid beta (Abeta) type in EL vesicles of affected neurons. EL modulating agents partially ameliorate the Abeta-mediated cell abnormalities. However, no extensive studies on the potential pharmaceutical applications of combinations of such agents and their synergistic effects have been performed. This study shows the beneficial anti-amyloid effects of several combinations of lysosomal modulators and other pharmacological and new nanobiotechnological agents. Some agents potentiated each other’s action and some of them facilitated the anti-amyloid actions of memantine, a modifier of Ca2+-permeable channels involved in AD and one of the few drugs used for treatment of AD. Another compound used in nanobiotechnology ameliorated as a nanocarrier the beneficial effects of some of these potential pharmaceutical agents. They may be considered as additional drugs to improve the efficacy of the therapeutic approaches for AD and related neurodegenerative disorders.

Keywords: Alzheimer’s disease, amyloid peptides, cell viability, endosomes, lysosomes, memantine, nanocarrier-assisted pharmacological approaches, lysosomal modulators, nanobiotechnology, therapeutic approaches