Neurobiology and therapeutic utility of neurotoxins targeting postsynaptic mechanisms of neuromuscular transmission

•Mechanisms of neurotransmission at the neuromuscular junction (NMJ).•Neurobiology of neurotoxins targeting post-synaptic mechanisms at the NMJ.•Therapeutic utility and translation of post-synaptic neurotoxins into medicine.•Perspective and key areas of future developments with the use of neurotoxins. The neuromuscular junction (NMJ) is the principal site for the translation of motor neurochemical signals to muscle activity. Therefore, the release and sensing machinery of acetylcholine (ACh) along with muscle contraction are two of the main targets of natural toxins and pathogens, causing paralysis. Given pharmacology and medical advances, the active ingredients of toxins that target postsynaptic mechanisms have become of major interest, showing promise as drug leads. Herein, we review key facets of prevalent toxins modulating the mechanisms of ACh sensing and generation of the postsynaptic response, with muscle contraction. We consider the correlation between their outstanding selectivity and potency plus effects on motor function, and discuss emerging data advocating their usage for the development of therapies alleviating neuromuscular dysfunction. This review presents the state-of-the-art for biological toxins targeting postsynaptic mechanisms of neurotransmission at the neuromuscular junction. It discusses emerging evidence for the therapeutic use of these biomolecules in the treatment of neuromuscular transmission disorders.