title: β-Amyloid-aluminum complex alters cytoskeletal stability and increases ROS production in cortical neurons.
abstract: Several lines of evidence have supported the potential involvement of metal ions in the etiology of Alzheimer's Disease (AD). However, the molecular mechanisms underlying this interaction are still partially unknown. Previous work from our laboratory has shown that β-amyloid peptide (Aβ) aggregation was strongly influenced by the conjugation of the peptide with few metal ions (aluminum, copper, zinc, and iron) that are found in high concentrations in the senile plaque core. The binding of aluminum (Al) to Aβ specifically stabilized the peptide in an oligomeric conformation. Here, we show that the aggregation of Aβ-Al was boosted by sodium dodecyl sulfate, a detergent that mimics some characteristics of biological membrane, suggesting a potential role for membrane components in the Aβ aggregation process. Notably, we also found that Aβ-Al caused mitochondrial dysfunction and reactive oxygen species production in primary cortical neurons. Aβ-Al strongly promoted also alterations in cytoskeleton network as shown by the increased F-actin expression and the occurrence of neuritic beading. Interestingly, the neurotoxic effect of this metal complex was associated with a decreased mRNA expression of ubiquitin thiolesterase, an ubiquitin-dependent protein involved in catabolic process, and by the increased expression of glutaminyl cyclase, responsible for pathological post-translational modification of Aβ. These results suggest that, in neuronal cells, Aβ-Al can induce relevant detrimental changes that resemble pathological hallmarks of AD.
authors: Department of Neurological, Neuropsychological, Morphological and Motor Sciences, Section of Physiology, University of Verona, Strada le Grazie 8, 37134 Verona, Italy. silvia.bolognin@univr.it
authors: Silvia
authors: S
authors: Bolognin
authors: Paolo
authors: P
authors: Zatta
authors: Erika
authors: E
authors: Lorenzetto
authors: Maria Teresa
authors: MT
authors: Valenti
authors: Mario
authors: M
authors: Buffelli
mesh_terms: D000535:Aluminum / Q000737:chemistry / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D042967:Electron Transport Complex I / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000201:enzymology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D012967:Sodium Dodecyl Sulfate; D000535:Aluminum; D042967:Electron Transport Complex I