Botulinum Neurotoxin Induces Neurotoxic Microglia Mediated by Exogenous Inflammatory Responses
Source abstract
Abstract
Abstract Botulinum neurotoxin serotype A (BoNT/A) is widely used in therapeutics and cosmetics. The effects of multi‐dosed BoNT/A treatment are well documented on the peripheral nervous system (PNS), but much less is known on the central nervous system (CNS). Here, the mechanism of multi‐dosed BoNT/A leading to CNS neurodegeneration is explored by using the 3D human neuron‐glia model. BoNT/A treatment reduces acetylcholine, triggers astrocytic transforming growth factor beta, and upregulates C1q, C3, and C5 expression, inducing microglial proinflammation. The disintegration of the neuronal microtubules is escorted by microglial nitric oxide, interleukin 1β, tumor necrosis factor α, and interleukin 8. The microglial proinflammation eventually causes synaptic impairment, phosphorylated tau (pTau) aggregation, and the loss of the BoNT/A‐treated neurons. Taking a more holistic approach, the model will allow to assess therapeutics for the CNS neurodegeneration under the prolonged use of BoNT/A.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Botulinum Toxin and Related Neurological Disorders · Parkinson's Disease Mechanisms and Treatments · Nerve injury and regeneration
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
School of Medicine University of California San Diego CA 92093 USA
Department of Mechanical Engineering and Engineering Sciences University of North Carolina Charlotte NC 28223 USA
Institute Quantum Biophysics Sungkyunkwan University, 2066 Seobu‐ro, Jangan‐gu Suwon Gyeonggi 16419 Republic of Korea
Department of Biophysics Sungkyunkwan University, 2066 Seobu‐ro, Jangan‐gu Suwon Gyeonggi 16419 Republic of Korea
Department of Intelligent Precision Healthcare Convergence Sungkyunkwan University, 2066 Seobu‐ro, Jangan‐gu Suwon Gyeonggi 16419 Republic of Korea
Botulinum Research Center, Institute of Advanced Sciences Dartmouth MA 02747 USA
Funding
National Research Foundation · National Institutes of Health · Ministry of Health and Welfare
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