조한상 (성균관대학교)

한빛사논문

조회231

성균관대학교

CV File 513 kb

Adv. Sci., Feb 11 2024, | https://doi.org/10.1002/advs.202305326 Botulinum Neurotoxin Induces Neurotoxic Microglia Mediated by Exogenous Inflammatory Responses

Ghuncha Ambrin ^1,2, You Jung Kang ^3,4, Khanh Van Do ^3,5, Charles Lee ², Bal Ram Singh ⁶, Hansang Cho^3,4,5

¹School of Medicine, University of California, San Diego, CA, 92093, USA.

²Department of Mechanical Engineering and Engineering Sciences, University of North Carolina, Charlotte, NC, 28223, USA.

³Institute Quantum Biophysics, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi, 16419, Republic of Korea.

⁴Department of Biophysics, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi, 16419, Republic of Korea.

⁵Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, Gyeonggi, 16419, Republic of Korea.

⁶Botulinum Research Center, Institute of Advanced Sciences, Dartmouth, MA, 02747, USA.

CORRESPONDING AUTHOR : Hansang Cho

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.

논문정보

형식Research article
게재일2024년 02월 (BRIC 등록일 2024-03-06)
연구진국내(교신)+국외 연구진
분야 바이오·의료융합 > 뇌인지과학

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