Alpha?Synuclein oligomerization and aggregation: All models are useful but only if we know what they model
نویسندگان
چکیده
Alpha-synuclein oligomerization is one of the early events on pathway to Lewy body formation. Therefore, interfering with this process holds tremendous potential for developing therapies that block ?-Syn pathology formation and toxicity. The development robust reliable cellular models alpha-synuclein important step toward achieving goal. Unlike fibrils, which can be detected labeled using multiple tools validated antibodies, oligomers are very difficult differentiate from soluble monomeric in cells. This has led increased reliance fusing fluorescent proteins or fragments thereof develop assays investigate oligomerization. We recently presented results highlight limitation these assays, Bimolecular Fluorescence (BIFC) assay (Frey et al. 2020b). Our findings underscored critical importance characterizing validating before their use mechanistic studies drug discovery studies. In commentary, I present my response Dr Tiago Outeiro's recent commentary work, expand our previous discussions BIFC assay, propose an integrated approach characterization, validation, improvements aggregation. Having access well-characterized essential not only advancing understanding biology PD but also identify novel therapeutic targets drugs could successfully developed into treatments synucleinopathies. more models, faster we likely achieve goals.
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ژورنال
عنوان ژورنال: Journal of Neurochemistry
سال: 2021
ISSN: ['0022-3042', '1471-4159']
DOI: https://doi.org/10.1111/jnc.15275