PLoS Genet: break the rules! Thrombin can degrade nerve cells!

March 17, 2019 / BIOON / - researchers of Sark Institute of biology accidentally found that thrombin can degrade nerves and also uncover the mechanism of protective effect of neuroglial cells (including Schwann cells) supporting nerves This study was published in PLoS In genetics, the study found that Schwann cells can protect nerve cells by inhibiting clotting proteins and other damaging enzymes released by muscle cells This work has an important impact on amyotrophic lateral sclerosis (ALS), multiple sclerosis, Alzheimer's disease or schizophrenia and other diseases Photo source: PLoS Genetics "this is the first discovery that thrombin, a coagulation related protein, plays a biological role outside the liver system and plays an important role in neurodegradation." Professor Kuo Fen Lee of the Sark Institute, the study's co-author, said "We further found that Schwann cells can fight thrombin to protect nerves These results are completely unexpected and pose interesting questions about the formation and maintenance of synapses in healthy and diseased conditions " Schwann cells form a protective insulator around the axon, which helps to form synapses and connections between nerve cells To learn more about the role of Schwann cells in neural health, the team studied a special synapse, the neuromuscular junction (NMJ), which is the interface between Schwann cells, neurons and muscles In the absence of Schwann cells, the NMJ synapses in the mouse model degraded after two days, demonstrating their role in synaptic growth The researchers found that in the absence of Schwann cells, acetylcholine, a signal molecule in NMJ, was the main culprit in neuronal degradation When the researchers went deeper, they found a mechanism that had not been found in the past: if acetylcholine was allowed to live and die, it would cause muscle cells to release a clotting protein called thrombin, which, together with other enzymes, would degrade nerves In healthy neurons, Schwann cells release molecules that block thrombin, thereby protecting synapses "We are surprised that Schwann cells can maintain the development of neuromuscular synapses by indirectly inhibiting the negative factors released by active muscles One of the factors is thrombin, whose most famous role is to form blood clots." Thomas Gould, a former Sark Institute researcher and lead author of the study, said In order to confirm the role of thrombin in NMJ, the researchers observed in a mouse model, which lacked thrombin, and found that the axon degradation of neurons in mice was less These results further confirm that thrombin plays a key role in the degradation of neuronal axons "This study provides new insights into the genetic and molecular pathways that alter synaptic development and maintenance." Lee said "The next step is to study the biological mechanism of thrombin and other factors destroying synapses, and the ultimate goal is to find new disease interventions to treat the diseases related to thrombin enrichment or dysfunction." Reference: Kuo Fen Lee et al Global cells maintain synapses by engaging an activity dependent regression protection signal PLoS Genetics (2019) Doi: 10.1371/journal.pgen.1007948