title: Effects of aluminium on β-amyloid (1-42) and secretases (APP-cleaving enzymes) in rat brain.
abstract: Chronic administration of aluminium has been proposed as an environmental factor that may affect some pathological changes related to neurotoxicity and Alzheimer's disease (AD). The abnormal generation and deposition of β-amyloid (Aβ) in senile plaques are hallmark features in the brains of AD patients. Furthermore, Aβ is generated by the sequential cleavage of the amyloid precursor protein (APP) via the APP cleaving enzyme (α-secretase, or β-secretase) and γ-secretase. In the present study, we investigated the modulation of Aβ deposition and neurotoxicity in aluminium-maltolate-treated (0, 15, 30, 45 mmol/kg body weight via intraperitoneal injection) in experimental rats. We measured Aβ1-40 and Aβ1-42 in the cortex and hippocampus in rat brains using ELISA. Subtypes of α-secretase, β-secretase, and γ-secretase, including ADAM9, ADAM10, ADAM17 (TACE), BACE1, presenilin 1 (PS1) and nicastrin (NCT), were determined using western blotting analyses. These results indicated that aluminium-maltolate induced an AD-like behavioural deficit in rats at 30 and 45 mmol/kg body weight. Moreover, the Aβ1-42 content increased significantly, both in the cortex and hippocampus, although no changes were observed in Aβ1-40. Furthermore, ADAM9, ADAM10, and ADAM17 decreased significantly; in contrast, BACE1, PS1, and NCT showed significant increase. Taken together, these results suggest that the changes in secretases may correlate to the abnormal deposition of Aβ by aluminium in rat brains.
authors.affiliation: School of Public Health, Shanxi Medical University, Taiyuan, 030001, Shanxi, China.
authors.forename: Linping
authors.initials: L
authors.lastname: Wang
authors.forename: Jiali
authors.initials: J
authors.lastname: Hu
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Lu
authors.forename: Qinli
authors.initials: Q
authors.lastname: Zhang
authors.forename: Qiao
authors.initials: Q
authors.lastname: Niu
mesh_terms: D000535:Aluminum / Q000378:metabolism* / Q000633:toxicity*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D000535:Aluminum; D053829:Amyloid Precursor Protein Secretases