Elba Villegas and Gerardo Corzo, biotechnology researchers at the Universidad Autonóma del Estado de Morelos and the Universidad Nacional Autonóma de Mexico, set the record straight about spiders
Elba Villegas and Gerardo Corzo, biotechnology researchers at the Universidad Auton?ma del Estado de Morelos and the Universidad Nacional Auton?ma de Mexico, set the record straight about spiders
Spiders are nature’s pest controllers. These eight-legged, web-forming arachnid predators are equipped with two venom glands full of valuable chemicals designed to kill insect prey. Such compounds, from small organic molecules to complex structures such as acylpolyamines, neuropeptides and enzymes, are precious ligands that target several biological receptors. Since insect receptors are not substantially different from those of humans and other mammals, the majority of the molecules contained in spider venom could also target human receptors.
The potential medical uses of spider venoms are largely due to their selectivity and affinity for ion channels [proteins that allow ions to cross cell membranes] and other receptors. This makes them suitable for studying cell function and for designing therapeutic drugs. As an example, the venom of the theraphosid Grammostola spatulata, from South America, contains a peptide, GsMtx-4, that blocks stretch-activated ion channels. These channels are sensitive to muscle contraction and blood pressure and play an important role in coordinating a heartbeat. Potentially, GsMtx-4 could be used to treat cardiac patients.
Peptides make up a substantial part of spider venom, and modulate ionic currents across Ca2+, Na+, or K+ ion channels. Some spider peptides can discriminate between ion channel subtypes and several will inhibit peripheral neurons, the nerve cells that are associated with supplying sensation to the skin and skeletal muscles. Spider toxins that block the neuronal Ca2+ ion channel could prove important for the treatment of chronic pain.
A special group of the spider peptides have a mixed hydrophilic-hydrophobic nature. These form a -helical structures that insert into cell membranes to form pores, resulting in loss of cell function. Although most of these peptides will destroy red blood cells, they could potentially be used in topical applications, such as antibacterial coatings for medical implants, in inhibiting the growth of oral bacteria associated with tooth decay and in treating skin infections.
Of all the venom components, the acylpolyamines represent the vast majority of the molecules in the mixture. These have been shown to suppress epileptic activity in brain tissue. They can also act as pain-killers, by blocking capsaicin receptor channels, non-selective cation channels in sensory neurons that respond to pain-causing stimuli. Moreover, brain damage caused by restricted blood flow, for example during a stroke, can be prevented with acylpolyamines. The compounds work by blocking Ca2+ ion channels or preventing glutamate release, both of which are implicated in neuronal death.
Finally, enzymes and large protein components of spider venoms are of special medical importance. For example, the neurotoxic protein a -latrotoxin, from the black widow spider, causes massive neurotransmitter release. Similarly, an active enzyme in the venom of the brown recluse spider is sphingomyelinase D, which degrades cell membranes and causes painful lesions to develop. Another component of the venom, hyaluronidase, belongs to a family of compounds that have shown medical potential as tumour treatments.
Most spider species are harmless to humans, so peptides or drug molecules from these spiders are likely to be safe. By modifying the molecular surfaces and active sites of peptides and enzymes from spiders it is possible to gain specificity and/or affinity for a given receptor. Acylpolyamines, peptides and enzymes from spider venoms represent an interesting source of molecules for the design of novel pharmaceutical drugs.
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