{'fraction_non_alphanumeric': 0.04025844930417495, 'fraction_numerical': 0.03578528827037773, 'mean_word_length': 5.989583333333333, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Effects of Aβ1−42 fibrils and of the tetrapeptide Pr‐IIGL on the phosphorylation state of the τ‐protein and on the α7 nicotinic acetylcholine receptor in vitro

In order to investigate the possible links connecting β‐amyloid (Aβ) accumulation, τ‐hyperphosphorylation and nicotinic receptor expression, rat embryonic primary hippocampal cultures were incubated with amyloidogenic peptides. Exposure to 0.5 µm fibrillar Aβ1−42 for 3 days caused retraction of dendrites, shrinkage of cell bodies and a decrease in the expression of microtubule‐associated proteins 2b (MAP2b), without affecting the total number of neurons and their viability. No impact on the τ‐phosphorylation sites Ser‐202, Thr231/Ser235, Ser262 and Ser396/Ser404 was found. The total number of homomeric α7‐nicotinic receptors (α7‐nAChRs) and their affinity for [125I]α‐bungarotoxin remained unaltered. Upon incubation with the putatively protective tetrapeptide propionyl–isoleucine–isoleucine–glycine–leucine (Pr‐IIGL), an analogue of the region [31–34] of Aβ, cell bodies were swollen in the region of the apical dendrite. These morphological alterations, different from those elicited by Aβ1−42, did not involve MAP2 expression changes. In contrast to Aβ1−42, Pr‐IIGL caused a massive hyperphosphorylation of the τ‐protein at Ser‐202 and at Ser396/Ser404. The total number of homomeric α7‐nAChRs and their affinity for [125I]α‐bungarotoxin were unaffected. In conclusion, the present results show a toxic effect of Aβ1−42 on the cytoskeletal structure at concentrations normally present in the brains of Alzheimer's disease patients, but raise some doubts about the role of Aβ1−42 fibrils as a direct trigger of τ‐hyperphosphorylation. The tetrapeptide Pr‐IIGL cannot be considered protective with regard to cell morphology. Although it prevents the Aβ1−42‐induced retraction of dendrites, it exhibits other toxic properties. The homomeric α7‐nAChRs were not affected either by Aβ1−42 incubation or by Pr‐IIGL‐induced τ‐hyperphosphorylation.