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Ovsepian, S.V. ; O'Leary, V.B.* ; Ayvazyan, N.M.* ; Al-Sabi, A.* ; Ntziachristos, V. ; Oliver Dolly, J.*

Neurobiology and therapeutic applications of neurotoxins targeting transmitter release.

Pharmacol. Ther. 193, 135-155 (2019)
Postprint DOI PMC
Open Access Green
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 pre synaptic 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. (C) 2018 Elsevier Inc. All rights reserved.
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Publication type Article: Journal article
Document type Review
Keywords Exocytosis ; Nano-carriers ; Therapeutic Targeting ; Presynaptic ; Molecular Medicine ; Drug Delivery ; Botulinum Neurotoxin ; Tetanus Toxin ; Snare Proteins; Eaton Myasthenic Syndrome; Motor-nerve Terminals; Toxin Type-a; Nicotinic Acetylcholine-receptor; Alpha-latrotoxin Releases; Amino-acid-sequences; Gene-related Peptide; Omega-agatoxin Iva; Snake-venom Toxins; Funnel-web Spider
Language
Publication Year 2019
Prepublished in Year 2018
HGF-reported in Year 2018
ISSN (print) / ISBN 0163-7258
e-ISSN 1879-016X
Journal Pharmacology & Therapeutics.
Quellenangaben Volume: 193, Issue: , Pages: 135-155 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, England
Reviewing status Peer reviewed
Institute(s) Institute of Biological and Medical Imaging (IBMI)
POF-Topic(s) 30205 - Bioengineering and Digital Health
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-505500-001
DOI 10.1016/j.pharmthera.2018.08.016
WOS ID WOS:000456227400011
Scopus ID 85053120552
PubMed ID 30149105
Erfassungsdatum 2018-09-05
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