Table 1.
Summary of effects of environmental exposures on BACE1.†
| Exposure | Alterations in BACE1 | References |
|---|---|---|
| Metals | ||
| Aluminium | Aluminium exposure increased BACE1 activity in aged New Zealand rabbits and rats, elevated BACE1 levels in rats, and increased BACE1 mRNA in rats and SH-SY5Y cells | (18–22,184–186) |
| Arsenic | Developmental exposure of rats to arsenic increased BACE1 enzymatic activity and BACE1 protein; gene expression of BACE-1 increased in astrocytes exposed to arsenic | (25,203,204) |
| Copper | Copper exposure upregulated BACE1 around Aβ plaques in mice and increased the transcription of BACE1 in PC12 cells BACE1 has a copper-binding site in its cytosolic domain; it competes with SOD1 for the interaction with CCS |
(26,27,48,49) |
| Iron | Ferrous ion exposure increased BACE1 mRNA and protein expression in PC12 cells and neuroblastoma cells. Iron treatment enhanced binding of APP to BACE1, without significant changes in the level of BACE1 in microglia. |
(28,29,201). |
| Lead | Developmental exposure to lead increased expression of BACE1 in monkeys while BACE1 mRNA and protein expression and BACE1 activity were also upregulated in rodents. | (23–25,258–260) |
| Manganese | Manganese exposure increased the transcription of BACE1 in PC12 cells | (27) |
| Silver nanoparticles | Silver nanoparticle exposure increased the protein expression of BACE1 | (32) |
| Zinc | Zinc exposure increased BACE1 in mice and SH-SY5Y cells | (205) |
| Pesticides, fungicides, herbicides | ||
| DDT | DDT exposure increased BACE1 levels in SH-SY5Y cells | (33) |
| Paraquat | Paraquat treatment altered BACE1 subcellular compartmentalization | (36) |
| Rotenone | Rotenone treatment facilitated BACE1 expression and activity | (34) |
| Residues of cyprodinil, mepanipyrim, and pyrimethanil | Cocktail of fungicide residues promoted the expression of BACE1 | (35) |
| Synthetics | ||
| BPA | BPA exposure has been shown to increase the level of BACE1 in SH-SY5Y cells | (227,228) |
| PFOS | Chronic high concentration PFOS exposure in mice increases BACE1 mRNA | (37) |
| Particulates | Chronic exposure of mice to particulate matter increased BACE1 protein levels | (38,39,261) |
| Dieatary toxins/toxicants | ||
| Acrolein | Chronic acrolein exposure increased protein levels of BACE1 in rats and HT22 cells | (44,45,193,255–257) |
| Advanced glycation end products | Pentosidine and GLAP upregulates BACE1 mRNA and protein expression | (43) |
| Heterocyclic aromatic amines | PhIP exposure for acute, sub-acute, and sub-chronic time point increased BACE1 in mice | (43) |
†
Abbreviations: BPA: Bisphenol A, CCS: Copper chaperone for superoxide dismutase-1 (SOD1), DDT: Dichlorodiphenyltrichloroethane, PFOS: Perfluorooctane sulfonate, PhIP: 2-Amino-1-methyl-6-phenylimidazo (4,5-b)pyridine