Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.69 (botulinum neurotoxin)
 1,901 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One specialization of vertebrate presynaptic neuronal membranes is their multifold enrichment in complex gangliosides, suggesting that these sialoglycolipids may play a major functional role in synaptic transmission. We tested this hypothesis directly by studying neuromuscular synapses of mice lacking complex gangliosides attributable to deletion of the gene coding for beta1,4 GalNAc-transferase (GM2/GD2 synthase), which catalyzes an early step in ganglioside synthesis. Our studies show that complex gangliosides are surprisingly redundant for regulated neurotransmitter release under normal physiological conditions. In contrast, we show that they are membrane receptors for both the paralytic botulinum neurotoxin type-A and human neuropathy-associated anti-ganglioside autoantibodies that arise through molecular mimicry with microbial structures. These data prove the critical importance of complex gangliosides in mediating pathophysiological events at the neuromuscular synapse.
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PMID:Complex gangliosides at the neuromuscular junction are membrane receptors for autoantibodies and botulinum neurotoxin but redundant for normal synaptic function. 1217 85

Neuropathic pain is typified by injuries to the peripheral and central nervous system and derives from such causes as cancer, diabetes, multiple sclerosis, post-herpetic neuralgia, physical trauma or surgery, and many others. Patients suffering neuropathic pain do not respond to conventional treatment with non-steroidal anti-inflammatory drugs and show a reduced sensitivity to opiates often associated with serious side effects. Recently, it has been demonstrated that botulinum neurotoxin serotype-A (BoNT/A) is able to induce analgesia in inflammatory pain conditions. The goal of this research was to test if BoNT/A was able to relieve also neuropathic pain symptoms. By using chronic constriction injury of the sciatic nerve, a mouse model of neuropathic pain, we observed that peripheral administration of BoNT/A strongly reduced the mechanical allodynia associated with this neuropathy. Remarkably, a single non-toxic dose of BoNT/A was sufficient to induce anti-allodynic effects, which lasted for at least 3 weeks. This result is particularly relevant since neuropathic pain is poorly treated by current drug therapies. This communication enlarges our knowledge on potentially new medical uses of BoNT/A in efforts to ameliorate human health conditions, with very important implications in the development of new pharmacotherapeutic approaches against neuropathic pain.
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PMID:Anti-allodynic efficacy of botulinum neurotoxin A in a model of neuropathic pain. 1721 63

Foodborne botulism is a serious condition caused by Clostridium botulinum neurotoxin. Clinically, botulism presents as bilateral cranial nerve neuropathy and descending paralysis. We report a unique presentation of botulism to remind clinicians of this potentially fatal condition. In this observational case report initial evaluation showed only esodeviation. This progressed to unilateral cranial nerve six (CN VI) paresis along with systemic signs. Clinical diagnosis was made based on in-depth history and concurrent symptoms in three other patients. Foodborne botulism presenting as diplopia and unilateral motility deficits is rare and can represent a diagnostic and therapeutic challenge to the ophthalmologist.
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PMID:Diplopia as the primary presentation of foodborne botulism. 2299 67

Human botulism is a severe disease characterized by flaccid paralysis and inhibition of certain gland secretions, notably salivary secretions, caused by inhibition of neurotransmitter release. Naturally acquired botulism occurs in three main forms: food-borne botulism by ingestion of preformed botulinum neurotoxin (BoNT) in food, botulism by intestinal colonization (infant botulism and intestinal toxemia botulism in infants above one year and adults), and wound botulism. A rapid laboratory confirmation of botulism is required for the appropriate management of patients. Detection of BoNT in the patient's sera is the most direct way to address the diagnosis of botulism. Based on previous published reports, botulinum toxemia was identified in about 70% of food-borne and wound botulism cases, and only in about 28% of infant botulism cases, in which the diagnosis is mainly confirmed from stool sample investigation. The presence of BoNT in serum depends on the BoNT amount ingested with contaminated food or produced locally in the intestine or wound, and the timeframe between serum sampling and disease onset. BoNT levels in patient's sera are most frequently low, requiring a highly sensitive method of detection. Mouse bioassay is still the most used method of botulism identification from serum samples. However, in vitro methods based on BoNT endopeptidase activity with detection by mass spectrometry or immunoassay have been developed and depending on BoNT type, are more sensitive than the mouse bioassay. These new assays show high specificity for individual BoNT types and allow more accurate differentiation between positive toxin sera from botulism and autoimmune neuropathy patients.
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PMID:Toxemia in Human Naturally Acquired Botulism. 3320 55