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Neurobiology and therapeutic applications of neurotoxins targeting transmitter release

SV. Ovsepian, VB. O'Leary, NM. Ayvazyan, A. Al-Sabi, V. Ntziachristos, JO. Dolly,

. 2019 ; 193 (-) : 135-155. [pub] 20180825

Language English Country Great Britain

Document type Journal Article, Research Support, Non-U.S. Gov't, Review

Persistent link   https://www.medvik.cz/link/bmc20006793

Synaptic transmission is a fundamental neurobiological process enabling exchange of signals between neurons as well as neurons and their non-neuronal effectors. The complex molecular machinery of the synaptic vesicle cycle and transmitter release has emerged and developed in the course of the evolutionary race, to ensure adaptive gain and survival of the fittest. In parallel, a generous arsenal of biomolecules and neuroactive peptides have co-evolved, which selectively target the transmitter release machinery, with the aim of subduing natural rivals or neutralizing prey. With advances in neuropharmacology and quantitative biology, neurotoxins targeting presynaptic mechanisms have attracted major interest, revealing considerable potential as carriers of molecular cargo and probes for meddling synaptic transmission mechanisms for research and medical benefit. In this review, we investigate and discuss key facets employed by the most prominent bacterial and animal toxins targeting the presynaptic secretory machinery. We explore the cellular basis and molecular grounds for their tremendous potency and selectivity, with effects on a wide range of neural functions. Finally, we consider the emerging preclinical and clinical data advocating the use of active ingredients of neurotoxins for the advancement of molecular medicine and development of restorative therapies.

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$a Ovsepian, Saak V $u Institute for Biological and Medical Imaging, Helmholtz Zentrum Munich, German Research Center for Environmental Health, Neuherberg, Germany; Munich School of Bioengineering, Technical University Munich, Munich, Germany; International Centre for Neurotherapeutics, Dublin City University, Dublin, Ireland; The National Institute of Mental Health, Topolová 748, Klecany, Czechia; Faculty of Medicine at Charles University, Prague, Czechia. Electronic address: saak.ovsepian@gmail.com.
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$a Synaptic transmission is a fundamental neurobiological process enabling exchange of signals between neurons as well as neurons and their non-neuronal effectors. The complex molecular machinery of the synaptic vesicle cycle and transmitter release has emerged and developed in the course of the evolutionary race, to ensure adaptive gain and survival of the fittest. In parallel, a generous arsenal of biomolecules and neuroactive peptides have co-evolved, which selectively target the transmitter release machinery, with the aim of subduing natural rivals or neutralizing prey. With advances in neuropharmacology and quantitative biology, neurotoxins targeting presynaptic mechanisms have attracted major interest, revealing considerable potential as carriers of molecular cargo and probes for meddling synaptic transmission mechanisms for research and medical benefit. In this review, we investigate and discuss key facets employed by the most prominent bacterial and animal toxins targeting the presynaptic secretory machinery. We explore the cellular basis and molecular grounds for their tremendous potency and selectivity, with effects on a wide range of neural functions. Finally, we consider the emerging preclinical and clinical data advocating the use of active ingredients of neurotoxins for the advancement of molecular medicine and development of restorative therapies.
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$a O'Leary, Valerie B $u International Centre for Neurotherapeutics, Dublin City University, Dublin, Ireland.
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$a Ayvazyan, Naira M $u Orbeli Institute of Physiology, National Academy of Sciences of the Republic of Armenia, Yerevan, Armenia.
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$a Al-Sabi, Ahmed $u College of Engineering and Technology, American University of the Middle East, Eqaila, Kuwait.
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$a Ntziachristos, Vasilis $u Institute for Biological and Medical Imaging, Helmholtz Zentrum Munich, German Research Center for Environmental Health, Neuherberg, Germany; Munich School of Bioengineering, Technical University Munich, Munich, Germany.
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$a Dolly, James O $u International Centre for Neurotherapeutics, Dublin City University, Dublin, Ireland. Electronic address: oliver.dolly@dcu.ie.
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