1. Inactivation of GAP-43 due to the depletion of cellular calcium by the Pb and amyloid peptide induced toxicity: An in vitro approach.
- Author
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Ayyalasomayajula N, Bandaru M, Dixit PK, Ajumeera R, Chetty CS, and Challa S
- Subjects
- Amyloid Precursor Protein Secretases genetics, Amyloid Precursor Protein Secretases metabolism, Aspartic Acid Endopeptidases genetics, Aspartic Acid Endopeptidases metabolism, Cell Differentiation drug effects, Cell Line, Tumor, Cell Survival drug effects, GAP-43 Protein genetics, Humans, Protein Kinase C genetics, Protein Kinase C metabolism, Synaptophysin genetics, Synaptophysin metabolism, Amyloid beta-Peptides toxicity, Calcium metabolism, GAP-43 Protein metabolism, Gene Expression Regulation drug effects, Lead toxicity
- Abstract
Environmental pollutant, Lead (Pb) is known to induce neurotoxicity in human. The central nervous system is the most vulnerable to the minute levels of Pb induced toxicity. Pb has been linked to Alzheimer's disease (AD) as a probable risk factor, as it shows epigenetic and developmental link associated with Alzheimer's disease-like pathology. Beta amyloid peptides were considered as the crucial factors in the beta amyloid plaque formation in Alzheimer's disease brain. In this context, we investigated the molecular mechanism involved in the development of Pb induced Alzheimer's disease in in vitro. Previous data from our studies have reported that Pb in the presence of beta Amyloid peptide (1-40) and (25-35) induces more apoptosis than individual exposures. Here, to further evaluate the molecular mechanism underlying Pb induced Alzheimer's disease; we focussed on the involvement of calcium signalling in inducing cell death. Our experimental observations suggesting that Pb in the presence of beta amyloid peptide alters intracellular calcium levels, which leads to the increased beta-secretase activity, which further promotes the generation of beta amyloid peptides. It also showed depression in the levels of GAP-43 expression, inhibition of PKC activity and altering synaptic activity further leads to cell death., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2020
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