Biotech R & D
- R & D Overview
- Inhibition of Secretion
- Creating Novel Proteins
- Therapeutic Potential
INHIBITION
OF CELL SECRETION
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Inhibition of Cell Secretion
Clostridial neurotoxins, including the botulinum neurotoxins (BoNTs), are proteases that selectively cut one of three proteins, the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins.
The SNARE proteins form a complex required for synaptic vesicles to fuse with the pre-synaptic membrane in nerve cells. By cutting one of the SNARE proteins the neurotoxins prevent formation of the SNARE complex and so block acetylcholine release from motor neurons and other peripheral cholinergic nerves. The neurotoxin enzyme activity, together with the SNARE protein cleavage product, can survive within the nerve terminals for prolonged periods, preventing formation of functional SNARE complexes and thereby inhibiting secretion. This underpins the prolonged therapeutic benefit achieved with clinical neurotoxin products.
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The SNARE complex is not restricted to nerve cells, indeed it represents a universal mechanism for vesicle fusion and secretion in eukaryotic cells and so proteolytic cleavage of SNARE proteins has the potential to inhibit vesicle fusion with the cell membrane in all eukaryotic cells. Vesicle fusion underpins both secretion, by which the contents of the vesicle are discharged to the outside of the cell, and the incorporation of proteins, such as receptors and ion channels, contained within the vesicle membrane into the cell membrane. The highly specific protease activity of clostridial neurotoxins is potentially capable of SNARE protein cleavage and inhibition of vesicle fusion and secretion in a wide range of cell types.
Key facts:
About Syntaxin's novel recombinant proteins:
- 1. They are highly selective and inhibit secretion only from target cells
- 2. They are capable of inhibiting secretion for prolonged periods
- 3. They are ideal for the treatment of certain chronic diseases
Due to their selectivity for peripheral neurons, particularly cholinergic neurons, however, the neurotoxins do not affect secretion from other cell types. The novel recombinant proteins produced by Syntaxin enable delivery of the neurotoxin enzyme activity to new target cells and so enable selective inhibition of vesicle fusion and secretion from the selected target cell.
Because the Syntaxin proteins incorporate the protease activity of the botulinum neurotoxins,
they are capable of inhibiting vesicle fusion and secretion in their target cell for prolonged
periods and therefore have therapeutic potential in the treatment of chronic diseases in which
the target secretion plays a pathophysiological role.
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