JAK inhibitors, the potential therapy against synaptic plasticity

Broad synaptic plasticity includes plasticity of synaptic transmission, synapticdevelopmental plasticity and synaptic morphology plasticity, generally without specialinstructions, referring to the plasticity of synaptic transmission. In recent years, the synaptic plasticity is the areas of research in the field of neuroscience, which has the fastest progress, and achieves most. Its main manifestations - long-term potentiation (LTP) and long-term depression(LTD), have been recognized as the biological basis of learning and memory activity at the cellular level. With the deepening of the relevant research, the plasticity of synaptic transmission has been found to be involved in the feeling, cardiovascular adjustment, and otherimportant physiological or pathological processes, in addition to the closely related with learning and memory function.

As we know, the JAK/STAT pathway has been reported to be involved in many physiological processes including those governing cell survival, proliferation, differentiation, development, and inflammation, once activated by cytokine receptors, growth-hormone like receptors and the leptin receptor. Recently, there are more evidences demonstrating that this pathway also has neuronal specific functions in the central nervous system (CNS), such as leptin-induced neuroprotection, Alzheimer’s disease and memory. For example, Ag490, a JAK kinase inhibitor has led to working memory impairment. The possible mechanism has been focus on in many studies, for example, both LTP and Ltd are caused by the synaptic activation of one class of glutamate receptor, the NMDA receptor, and are expressed as alterations in synaptic transmission mediated by another class of glutamate receptor, the AMPA receptor.

In this post, I will pay close attention to something different, the anti-tumor chemotherapy drugs.

Accompanied by the production of anti-tumor effects effectively, these drugs would also produce some side effects. For example, paclitaxel, oxaliplatin, and other chemotherapeutic agents will produce chronic, bilaterally symmetrical, sensory, peripheral neuropathies often accompanied by neuropathic pain. Clinical descriptions of these neuropathies suggest that they produce similar neuropathic pain states. Neuropathic pain is defined as pain syndrome caused by primary lesion or dysfunction of central or peripheral nervous system, and may be divided into peripheral neuropathic pain, central neuropathic pain, or mixed (peripheral and central) neuropathic pain. At present, Up to 7% to 8% of the European population is suffering from the disease and about 5% of persons may have a severe symptom. However, neuropathic pain has been troubling medical researchers: the pathogenesis is unclear. In recent years, with the development of molecular biology and electrophysiological technology, researchers have gradually in-depth understood the complexity pathogenesis of neuropathic pain, which provides new ideas and methods for the treatment of neuropathic pain.

In some reports, chemotherapy-induced damage to mitochondria in primary afferent sensory axons is considered s the possible mechanism to result in a chronic energy deficiency that is the proximate cause of the symptoms of the neuropathy. Paclitaxel-evoked and oxaliplatin-evoked painful neuropathies in peripheral nerve cells are observed to be associated with decreased respiration and ATP production caused by chronic deficits of mitochondrial function.

Numerologist Warda is hooked on OG-L002 fishing, collecting. And lastly her encouragement comes from socializing along with her companions.