Exploiting Botulinum Neurotoxins for the Study of Brain Physiology and Pathology
Botulinum neurotoxins are metalloproteases that specifically cleave N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins in synaptic terminals, resulting in a potent inhibition of vesicle fusion and transmitter release. The family comprises different serotypes (BoNT/A to Bo...
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-04-01
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| Series: | Toxins |
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| Online Access: | http://www.mdpi.com/2072-6651/10/5/175 |
| _version_ | 1811304502102327296 |
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| author | Matteo Caleo Laura Restani |
| author_facet | Matteo Caleo Laura Restani |
| author_sort | Matteo Caleo |
| collection | DOAJ |
| description | Botulinum neurotoxins are metalloproteases that specifically cleave N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins in synaptic terminals, resulting in a potent inhibition of vesicle fusion and transmitter release. The family comprises different serotypes (BoNT/A to BoNT/G). The natural target of these toxins is represented by the neuromuscular junction, where BoNTs block acetylcholine release. In this review, we describe the actions of botulinum toxins after direct delivery to the central nervous system (CNS), where BoNTs block exocytosis of several transmitters, with near-complete silencing of neural networks. The use of clostridial neurotoxins in the CNS has allowed us to investigate specifically the role of synaptic activity in different physiological and pathological processes. The silencing properties of BoNTs can be exploited for therapeutic purposes, for example to counteract pathological hyperactivity and seizures in epileptogenic brain foci, or to investigate the role of activity in degenerative diseases like prion disease. Altogether, clostridial neurotoxins and their derivatives hold promise as powerful tools for both the basic understanding of brain function and the dissection and treatment of activity-dependent pathogenic pathways. |
| first_indexed | 2024-04-13T08:08:17Z |
| format | Article |
| id | doaj.art-ab4cff2ce697439e9d9914ac80b1aec6 |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-13T08:08:17Z |
| publishDate | 2018-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-ab4cff2ce697439e9d9914ac80b1aec62022-12-22T02:55:06ZengMDPI AGToxins2072-66512018-04-0110517510.3390/toxins10050175toxins10050175Exploiting Botulinum Neurotoxins for the Study of Brain Physiology and PathologyMatteo Caleo0Laura Restani1CNR Neuroscience Institute, via G. Moruzzi 1, 56124 Pisa, ItalyCNR Neuroscience Institute, via G. Moruzzi 1, 56124 Pisa, ItalyBotulinum neurotoxins are metalloproteases that specifically cleave N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins in synaptic terminals, resulting in a potent inhibition of vesicle fusion and transmitter release. The family comprises different serotypes (BoNT/A to BoNT/G). The natural target of these toxins is represented by the neuromuscular junction, where BoNTs block acetylcholine release. In this review, we describe the actions of botulinum toxins after direct delivery to the central nervous system (CNS), where BoNTs block exocytosis of several transmitters, with near-complete silencing of neural networks. The use of clostridial neurotoxins in the CNS has allowed us to investigate specifically the role of synaptic activity in different physiological and pathological processes. The silencing properties of BoNTs can be exploited for therapeutic purposes, for example to counteract pathological hyperactivity and seizures in epileptogenic brain foci, or to investigate the role of activity in degenerative diseases like prion disease. Altogether, clostridial neurotoxins and their derivatives hold promise as powerful tools for both the basic understanding of brain function and the dissection and treatment of activity-dependent pathogenic pathways.http://www.mdpi.com/2072-6651/10/5/175synaptic transmissionSNAP-25epilepsyParkinson’s diseaseneurotransmission blockadeelectrical activityprion disease |
| spellingShingle | Matteo Caleo Laura Restani Exploiting Botulinum Neurotoxins for the Study of Brain Physiology and Pathology Toxins synaptic transmission SNAP-25 epilepsy Parkinson’s disease neurotransmission blockade electrical activity prion disease |
| title | Exploiting Botulinum Neurotoxins for the Study of Brain Physiology and Pathology |
| title_full | Exploiting Botulinum Neurotoxins for the Study of Brain Physiology and Pathology |
| title_fullStr | Exploiting Botulinum Neurotoxins for the Study of Brain Physiology and Pathology |
| title_full_unstemmed | Exploiting Botulinum Neurotoxins for the Study of Brain Physiology and Pathology |
| title_short | Exploiting Botulinum Neurotoxins for the Study of Brain Physiology and Pathology |
| title_sort | exploiting botulinum neurotoxins for the study of brain physiology and pathology |
| topic | synaptic transmission SNAP-25 epilepsy Parkinson’s disease neurotransmission blockade electrical activity prion disease |
| url | http://www.mdpi.com/2072-6651/10/5/175 |
| work_keys_str_mv | AT matteocaleo exploitingbotulinumneurotoxinsforthestudyofbrainphysiologyandpathology AT laurarestani exploitingbotulinumneurotoxinsforthestudyofbrainphysiologyandpathology |