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Botulinum neurotoxins A, B, C, E, and F preferentially enter cultured human motor neurons compared to other cultured human neuronal populations
Author(s) -
Pellett Sabine,
Tepp William H.,
Johnson Eric A.
Publication year - 2019
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13508
Subject(s) - motor neuron , synapsin i , biology , neuron , synapsin , glutamatergic , receptor , gabaergic , dopaminergic , microbiology and biotechnology , induced pluripotent stem cell , neuroscience , dopamine , biochemistry , glutamate receptor , spinal cord , gene , synaptic vesicle , vesicle , embryonic stem cell , membrane
Human‐induced pluripotent stem cell (hi PSC )‐derived neurons can be exquisitely sensitive to botulinum neurotoxins (Bo NT s), exceeding sensitivity of the traditionally used mouse bioassay. In this report, four defined hi PSC ‐derived neuronal populations including primarily GABA ergic, glutamatergic, dopaminergic, and motor neurons were examined for Bo NT /A, B, C, D, E, and F sensitivity. The data indicate that sensitivity varies markedly for the Bo NT s tested. Motor neurons are significantly more sensitive than other neuron types for all Bo NT s except Bo NT /D. Examination of SNARE protein levels and Bo NT ‐specific cell surface protein receptors reveals few differences between the cell types except greater expression levels of the receptor protein SV 2C and synapsin‐ II a in motor neurons. This indicates that differential toxicity of Bo NT s for motor neurons compared to other neuronal cell types involves multiple mechanisms.