Nanoengineered on-demand drug delivery system improves efficacy of pharmacotherapy for epilepsy

Wu, Di; Fan, Fudong; Zhang, Qi; Wang, Xia; Gong, Yitao; Chen, Xiaojie; Zheng, Yuyi; Tan, Bei; Xu, Cenglin; Xie, Hujun; Fang, Wenjun; Chen, Zhong; Wang, Yi

doi:10.1126/sciadv.abm3381

Cited by 45 publications

(31 citation statements)

References 41 publications

(49 reference statements)

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“…Epileptic seizures are generally caused by abnormal, excessive, and synchronous neuronal activity in the brain. 44 As Fig. 3(j) shows, on the single cellular scale, action potential travels along the axon to the synapse, where voltage-gated calcium channels open, and neurotransmitters with excitatory or inhibitory function are released into the synaptic cleft.…”

Section: Resultsmentioning

confidence: 99%

A mechanically adaptive hydrogel neural interface based on silk fibroin for high-efficiency neural activity recording

et al. 2022

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Section: Resultsmentioning

confidence: 99%

A mechanically adaptive hydrogel neural interface based on silk fibroin for high-efficiency neural activity recording

et al. 2022

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“…EEG signals were band-pass filtered spanning DC to 200 Hz and sampled at 2 kHz using an amplifier (Neuroscan System). EEG recordings were continued for 30 min after PTZ injection [ 18 , 33 ].…”

Section: Methodsmentioning

confidence: 99%

A patient-derived mutation of epilepsy-linked LGI1 increases seizure susceptibility through regulating Kv1.1

Zhou

Wang

et al. 2023

Cell Biosci

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Background Autosomal dominant lateral temporal epilepsy (ADLTE) is an inherited syndrome caused by mutations in the leucine-rich glioma inactivated 1 (LGI1) gene. It is known that functional LGI1 is secreted by excitatory neurons, GABAergic interneurons, and astrocytes, and regulates AMPA-type glutamate receptor-mediated synaptic transmission by binding ADAM22 and ADAM23. However, > 40 LGI1 mutations have been reported in familial ADLTE patients, more than half of which are secretion-defective. How these secretion-defective LGI1 mutations lead to epilepsy is unknown. Results We identified a novel secretion-defective LGI1 mutation from a Chinese ADLTE family, LGI1-W183R. We specifically expressed mutant LGI1W183R in excitatory neurons lacking natural LGI1, and found that this mutation downregulated Kv1.1 activity, led to neuronal hyperexcitability and irregular spiking, and increased epilepsy susceptibility in mice. Further analysis revealed that restoring Kv1.1 in excitatory neurons rescued the defect of spiking capacity, improved epilepsy susceptibility, and prolonged the life-span of mice. Conclusions These results describe a role of secretion-defective LGI1 in maintaining neuronal excitability and reveal a new mechanism in the pathology of LGI1 mutation-related epilepsy.

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“…Based on specific reaction mechanisms, certain materials go through phase transition or depolymerization in response to biological signals of NDs and release the loading drugs in lesions timely and precisely. These [70] Copyright 2022, The Authors. Published by American Association for the Advancement of Science.…”

Section: Transmission-free Responsive Systemsmentioning

confidence: 99%

Advanced Temporally‐Spatially Precise Technologies for On‐Demand Neurological Disorder Intervention

2023

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Temporal‐spatial precision has attracted increasing attention for the clinical intervention of neurological disorders (NDs) to mitigate adverse effects of traditional treatments and achieve point‐of‐care medicine. Inspiring steps forward in this field have been witnessed in recent years, giving the credit to multi‐discipline efforts from neurobiology, bioengineering, chemical materials, artificial intelligence, and so on, exhibiting valuable clinical translation potential. In this review, the latest progress in advanced temporally‐spatially precise clinical intervention is highlighted, including localized parenchyma drug delivery, precise neuromodulation, as well as biological signal detection to trigger closed‐loop control. Their clinical potential in both central and peripheral nervous systems is illustrated meticulously related to typical diseases. The challenges relative to biosafety and scaled production as well as their future perspectives are also discussed in detail. Notably, these intelligent temporally‐spatially precision intervention systems could lead the frontier in the near future, demonstrating significant clinical value to support billions of patients plagued with NDs.

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Nanoengineered on-demand drug delivery system improves efficacy of pharmacotherapy for epilepsy

Abstract: Electroresponsive and synergistic brain-targeting nanoparticles improve efficacy of pharmacotherapy for epilepsy.

Cited by 45 publications

References 41 publications

A mechanically adaptive hydrogel neural interface based on silk fibroin for high-efficiency neural activity recording

A mechanically adaptive hydrogel neural interface based on silk fibroin for high-efficiency neural activity recording

A patient-derived mutation of epilepsy-linked LGI1 increases seizure susceptibility through regulating Kv1.1

Advanced Temporally‐Spatially Precise Technologies for On‐Demand Neurological Disorder Intervention

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