Introduction:<\/b>\u00a0Alpha-synuclein (\u03b1-Syn) aggregation, transmission, and contribution to neurotoxicity represent central mechanisms underlying Parkinson\u2019s disease. The plant alkaloid \u201cnicotine\u201d was reported to attenuate \u03b1-Syn aggregation in different models, but its precise mode of action remains unclear.<\/p>\n
Methods:<\/b>\u00a0In this study, we investigated the effect of 2-week chronic nicotine treatment on \u03b1-Syn aggregation, neuroinflammation, neurodegeneration, and motor deficits in D-line \u03b1-Syn transgenic mice. We also established a novel humanized neuronal model of \u03b1-Syn aggregation and toxicity based on treatment of dopaminergic neurons derived from human induced pluripotent stem cells (iPSC) with \u03b1-Syn preformed fibrils (PFF) and applied this model to investigate the effects of nicotine and other compounds and their modes of action.<\/p>\n
Results and discussion:<\/b>\u00a0Overall, our results showed that nicotine attenuated \u03b1-Syn-provoked neuropathology in both models. Moreover, when investigating the role of nicotinic acetylcholine receptor (nAChR) signaling in nicotine\u2019s neuroprotective effects in iPSC-derived dopaminergic neurons, we observed that while \u03b14-specific antagonists reduced the nicotine-induced calcium response, \u03b14 agonists (e.g., AZD1446 and anatabine) mediated similar neuroprotective responses against \u03b1-Syn PFF-provoked neurodegeneration. Our results show that nicotine attenuates \u03b1-Syn-provoked neuropathology\u00a0in vivo<\/i>\u00a0and in a humanized neuronal model of synucleinopathy and that activation of \u03b14\u03b22 nicotinic receptors might mediate these neuroprotective effects.<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[44],"resource_type":[75],"application_areas":[50,53,76,77],"therapeutic_areas":[55,143],"target_categories":[337],"target_families":[360],"targets":[194],"resource_keyword":[],"class_list":["post-13290","resource_library","type-resource_library","status-publish","hentry","products_tags-patchliner","resource_type-publication","application_areas-ion-channels","application_areas-assay-development-and-validation","application_areas-drug-discovery","application_areas-cell-ipscs-profiling","therapeutic_areas-cns","therapeutic_areas-assay-development-and-validation","target_categories-ligand-gated-ion-channels","target_families-nicotinic-acetylcholine-receptors","targets-achr-4-2"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library\/13290","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/media?parent=13290"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/products_tags?post=13290"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_type?post=13290"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/application_areas?post=13290"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/therapeutic_areas?post=13290"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_categories?post=13290"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/target_families?post=13290"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/targets?post=13290"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/zh-hans\/wp-json\/wp\/v2\/resource_keyword?post=13290"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}