MMP-13 Enzyme and Neuropathy
In this article, we’ll examine the part of the MMP-13 enzyme in neuropathic pain and how it may be able to treat diabetic neuropathy. We will also touch on the role of annexin A2, TLR4, and lysozyme. We’ll also discuss how the MMP-13 enzyme can regulate the immune system. But first, let’s bring a peek at how the enzyme interacts with TLR4 and annexin A2.
The increased lysozyme levels
The increased lysozyme levels in nerve tissue in neurodegenerative diseases have been linked to pain. It’s also been shown to play a role in developing chronic pain. Lysozyme is an important mediator of pain and is a potential treatment for chronic nerve pain. Neuronal TLR4 and lysozyme have been shown to interact with each other during nerve injury.
In one study, MMP-12 expression was increased in neuropathic pain animal models. In addition, this enzyme is a potential target for IONP-enhanced MRI in injured spinal nerves. Moreover, further research is needed to determine whether these enzymes are associated with neuropathy. Currently, however, there are a few possible biomarkers that may help in the diagnosis of neuropathic pain.
Several drugs have been proven to affect the activity of MMP-13. One, paclitaxel, is a chemotherapeutic agent that damages nerves in patients with cancer. However, blocking the activity of MMP-13 can help improve skin defects and reverse chemotherapy-induced nerve damage. The chemotherapeutic agent also inhibits the production of lysozyme, which can cleave collagen.
Expression of inflammatory factors
The expression of inflammatory factors in the spinal cord and dorsal root ganglia is a common consequence of nerve injury and tissue inflammation. Several inflammatory cytokines affect neuronal excitability and contribute to the accelerated development of neuropathic pain. Inflammatory factors are regulated by intracellular signaling pathways and may contribute to neuropathic pain.
Researchers have linked MMP-13 to various diseases and are testing whether it is involved in peripheral neuropathy. They have found that over-expression of MMP-13 leads to a variety of nerve degeneration in mammalian models. Further, they are developing drugs targeting this enzyme that may improve peripheral neuropathy. These drugs may also provide other health benefits. These findings are currently being tested in a clinical trial.
The research has been published in two neuroscience journals: Neurosci Lett and Int J. Neurosci. Ohtori S, Takahashi K, and Myers RR have identified a connection between spinal annexin A2 and MMP-13 enzymes and peripheral neuropathy. In addition, the researchers noted that annexin A2 and map 13 were associated with decreased pain in mice and increased inflammation in rats.
A link between TLR4 and MMP13
Recent research indicates a link between TLR4 and MMP13 enzyme expression in the brain and the early development of neuropathy. This connection may be due to the way TLR signaling affects immune recruitment. However, more studies are needed to establish the precise link. This study was conducted on humans. It is necessary to cite that it is not clear whether TLR4 and MMP13 enzymes are directly linked to neuropathy.
Lysozyme is an enzyme found in the innate immune system linked to neuropathic pain. This enzyme increases the spontaneous activity of neurons in the spinal cord dorsal horn in rodents and is associated with inflammatory processes. However, additional analysis is needed to confirm the association between lysozyme and neuropathic pain despite these associations.
The researchers believe that lowering MMP-13 levels may help patients with peripheral neuropathy. To make this work more relevant to humans, they have developed a new drug that inhibits the over-expression of MMP-13 in cells. The compound is currently being tested in animal models to determine whether or not it works in human patients. If it does, it may have wider health implications. The study also shows that pharmacological treatments for peripheral neuropathy could have many other benefits.
Mechanisms of lysozyme-mediated neuropathic pain
In an empirical sample of neuropathic pain, the enzyme lysozyme is overexpressed in mice. It inhibits this enzyme by the compound chitobiose or silencing the lysozyme gene, resulting in a pain-free state. In another study, rats bathed in lysozyme stimulated nerves in the spinal cord, a mechanism that may explain the sensitivity of neuropathic pain.
Lysozyme is known to break down the cell walls of bacteria, but it is not the segment responsible for neuropathic pain. Lysozyme is thought to recruit another protein known as annexin 2A, which activates the immune system receptor TLR4 and promotes neuropathic pain. It also recruits another protein, IL-17, to the nerve.
Recent studies have revealed that lysozyme recruits annexin A2 to activate TLR4, a key player in lysozyme-mediated neuropathic pain. However, lysozyme can’t bind to TLR4 on its own, and the annexin-lysozyme complex is required to produce the pain-promoting effect in mice and rats.
Neuropathy to the MMP-13 enzyme
Scientists have linked peripheral neuropathy to the MMP-13 enzyme. This enzyme is responsible for degrading collagen, the protein that holds skin cells together. This degradation results in the degeneration of sensory nerve endings, a precursor to peripheral neuropathy. The compounds Rieger has discovered inhibit MMP-13 activity, making them promising therapeutic candidates. If they prove successful, these compounds could have numerous health benefits.
The paclitaxel molecule-induced peripheral neuropathy was identified in the zebrafish as a potential target for MMP-13. The scientists are now working on the underlying mechanisms of paclitaxel activation and MMP-13 activation in the epidermis. They also seek to determine how paclitaxel triggers neuropathy by inhibiting MMP-13. In addition, they are developing MMP-13 inhibitors for clinical applications. Since MMP-13 is responsible for axon degeneration in diabetic patients, further research will focus on the connection between diabetes and neuropathy.
Rieger and colleagues have identified two compounds that prevent or reverse peripheral neuropathy in zebrafish. They will now work with scientists at the University of New England to test these compounds in rats. These rats are closely related to humans, and this work could pave the way for human trials. In the meantime, it is essential to cite that diabetes is the leading cause of peripheral neuropathy, and this disease is a major health concern in many countries.
A new study reveals a link between mitochondrial dysfunction and the development of neuropathy. The study results show that defective mitochondrial filamentation and division lead to degeneration of the small fibers responsible for pain perception in the peripheral nervous system. The findings suggest that chemotherapy and anti-HIV drugs may trigger painful neuropathies by reducing mitochondrial respiration. Recent findings indicate that a dysfunctional mitochondrial structure in Schwann cells may contribute to the degeneration of pain-sensing neurons.
A genetic test reveals that mutations in a gene encoding gigaxonin increase the formation of large aggregates of intermediate filaments in neurons and fibroblasts—the fibroblasts of patients with giant axonal neuropathy (GAN) exhibit altered mitochondrial distribution. In addition, vimentin IF aggregates is associated with IF bundles. Moreover, mice expressing wild-type gigaxonin reduce these aggregates and restore mitochondrial motility.
The mutation in the Bb2 gene is responsible for the resistance of these mice to peripheral neuropathy in both type-1 and type-2 diabetes models. This suggests that Bb2 is a potential drug target in PDN. This protein also acts as a neuron-specific Drp1 activator. In the meantime, the research team plans to study the relationship between mitochondrial fragmentation and neuropathy. The aim is to investigate whether preventing mitochondrial fragmentation prevents damage to peripheral axons in patients with diabetes.
Mechanisms of paclitaxel-induced peripheral neuropathy
Approximately 70 percent of patients receiving chemotherapy experience paclitaxel-induced peripheral neuropathies. Its effect on peripheral nerves results from a process known as ion channel inhibition. The drugs are known to damage epidermal cells and induce degeneration of axons. The neuropathy may manifest as pain, numbness, temperature sensitivity, or both.
Cryotherapy and hypothermia have been shown to alleviate taxane-induced peripheral neuropathy in cancer patients. These treatments have also been shown to alleviate neuropathy induced by chemotherapy. Studies conducted by Hanai A, Ishiguro H, and Sozu T showed that using goshajinkigan and fatty acids may prevent or reduce chemotherapy-induced peripheral neuropathy.
Minocycline has been shown to protect against taxane-induced neuropathy in rats. Several studies have also shown that acetyl-L-carnitine supplementation protects against paclitaxel-induced neuropathy. Further, antioxidants such as glutathione and acetyl-L-carnitine can protect against paclitaxel-induced neuropathy.