title: Establishing the links between Aβ aggregation and cytotoxicity in vitro using biophysical approaches.
abstract: Aggregation and fibril formation of the amyloid-β (Aβ) peptides play a pivotal role in the pathogenesis of Alzheimer's disease (AD). The missing links on the pathway to Aβ oligomerization, fibril formation, and neurotoxicity in AD remain the identity of the toxic Aβ species and mechanism(s) of their toxicity. Such information is crucial for the development of mechanism-based therapeutics to treat AD and tools to diagnose and/or monitor the disease progression. Herein, we describe a simple approach that combines standard biophysical methods with cell biology assays to correlate the aggregation state of Aβ peptides with their cytotoxicity in vitro. The individual assays are well-established, commonly used, rely on easily accessible materials and can be performed within 24 h.
authors.affiliation: Laboratory of Molecular and Chemical Biology of Neurodegeneration, Brain Mind Institute, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland. asad.qureshi@epfl.ch
authors.forename: Asad
authors.initials: A
authors.lastname: Jan
authors.forename: Hilal A
authors.initials: HA
authors.lastname: Lashuel
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000633:toxicity*; D000818:Animals; D052160:Benzothiazoles; D001681:Biological Assay / Q000379:methods*; D055592:Biophysical Phenomena; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D016716:PC12 Cells; D010446:Peptide Fragments / Q000737:chemistry* / Q000633:toxicity*; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D051381:Rats; D013844:Thiazoles / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D010446:Peptide Fragments; D013844:Thiazoles; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C009462:thioflavin T; D007770:L-Lactate Dehydrogenase