PMC:6610326 / 70433-72641
Annnotations
{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/6610326","sourcedb":"PMC","sourceid":"6610326","source_url":"https://www.ncbi.nlm.nih.gov/pmc/6610326","text":"Conversely, aberrant expression of axon repulsion factors near the NMJ may contribute to neurodegeneration in ALS. Sema3A and its receptor neuropilin 1 (Nrp1) are involved in axon guidance during neural development (Huber et al., 2005; Moret et al., 2007). Sema3A is specifically upregulated in terminal Schwann cells near NMJs of vulnerable FF muscle fibers in mutant SOD1G93A mice (De Winter et al., 2006). Nrp1 is upregulated in axon terminals of the NMJ in this model and administration of an antibody against the Sema3A-binding domain of Nrp1 delayed the decline of motor functions while prolonging the lifespan of SOD1G93A mice (Venkova et al., 2014). Furthermore, Sema3A is upregulated in the motor cortex of ALS patients (Körner et al., 2016; Birger et al., 2018), but not in the spinal cord. Sema3A induces death of sensory, sympathetic, retinal and cortical neurons (Shirvan et al., 2002; Ben-Zvi et al., 2008; Jiang et al., 2010; Wehner et al., 2016), but not spinal neurons (Molofsky et al., 2014; Birger et al., 2018). Similarly, Sema3A induces apoptosis of human cortical neurons but promotes survival of spinal MNs (Birger et al., 2018). Furthermore, loss of Sema3A-expressing astrocytes in the ventral spinal cord leads to selective degeneration of α-MNs, but not γ-MNs (Hochstim et al., 2008; Molofsky et al., 2014). These data indicate that whilst Sema3A and Nrp1 contribute to the loss of MNs in ALS, some neuronal subpopulations are more susceptible than others. There is also evidence that other axon guidance proteins are associated with the susceptibility of MNs in ALS. Increased expression of ephrin A1 has been demonstrated in the vulnerable spinal MNs of ALS patients (Jiang et al., 2005). EPHA4, which is a disease modifier in zebrafish, rodent models and human ALS, encodes an Eph receptor tyrosine kinase, which is involved in axonal repulsion during development and in synapse formation, plasticity and memory in adults (Van Hoecke et al., 2012). The more vulnerable MNs express higher levels of EPHA4, and neuromuscular re-innervation is inhibited by Epha4. In ALS patients, EPHA4 expression also inversely correlates with disease onset and survival (Van Hoecke et al., 2012).","tracks":[{"project":"2_test","denotations":[{"id":"31316328-16364899-38515735","span":{"begin":230,"end":234},"obj":"16364899"},{"id":"31316328-18039974-38515736","span":{"begin":250,"end":254},"obj":"18039974"},{"id":"31316328-16677822-38515737","span":{"begin":402,"end":406},"obj":"16677822"},{"id":"31316328-24918638-38515738","span":{"begin":651,"end":655},"obj":"24918638"},{"id":"31316328-26921371-38515739","span":{"begin":745,"end":749},"obj":"26921371"},{"id":"31316328-29449528-38515740","span":{"begin":766,"end":770},"obj":"29449528"},{"id":"31316328-12376549-38515741","span":{"begin":893,"end":897},"obj":"12376549"},{"id":"31316328-19020035-38515742","span":{"begin":915,"end":919},"obj":"19020035"},{"id":"31316328-20133938-38515743","span":{"begin":935,"end":939},"obj":"20133938"},{"id":"31316328-27143756-38515744","span":{"begin":956,"end":960},"obj":"27143756"},{"id":"31316328-24776795-38515745","span":{"begin":1004,"end":1008},"obj":"24776795"},{"id":"31316328-29449528-38515746","span":{"begin":1025,"end":1029},"obj":"29449528"},{"id":"31316328-29449528-38515747","span":{"begin":1146,"end":1150},"obj":"29449528"},{"id":"31316328-18455991-38515748","span":{"begin":1304,"end":1308},"obj":"18455991"},{"id":"31316328-24776795-38515749","span":{"begin":1327,"end":1331},"obj":"24776795"},{"id":"31316328-15668976-38515750","span":{"begin":1710,"end":1714},"obj":"15668976"},{"id":"31316328-22922411-38515751","span":{"begin":1971,"end":1975},"obj":"22922411"},{"id":"31316328-22922411-38515752","span":{"begin":2202,"end":2206},"obj":"22922411"}],"attributes":[{"subj":"31316328-16364899-38515735","pred":"source","obj":"2_test"},{"subj":"31316328-18039974-38515736","pred":"source","obj":"2_test"},{"subj":"31316328-16677822-38515737","pred":"source","obj":"2_test"},{"subj":"31316328-24918638-38515738","pred":"source","obj":"2_test"},{"subj":"31316328-26921371-38515739","pred":"source","obj":"2_test"},{"subj":"31316328-29449528-38515740","pred":"source","obj":"2_test"},{"subj":"31316328-12376549-38515741","pred":"source","obj":"2_test"},{"subj":"31316328-19020035-38515742","pred":"source","obj":"2_test"},{"subj":"31316328-20133938-38515743","pred":"source","obj":"2_test"},{"subj":"31316328-27143756-38515744","pred":"source","obj":"2_test"},{"subj":"31316328-24776795-38515745","pred":"source","obj":"2_test"},{"subj":"31316328-29449528-38515746","pred":"source","obj":"2_test"},{"subj":"31316328-29449528-38515747","pred":"source","obj":"2_test"},{"subj":"31316328-18455991-38515748","pred":"source","obj":"2_test"},{"subj":"31316328-24776795-38515749","pred":"source","obj":"2_test"},{"subj":"31316328-15668976-38515750","pred":"source","obj":"2_test"},{"subj":"31316328-22922411-38515751","pred":"source","obj":"2_test"},{"subj":"31316328-22922411-38515752","pred":"source","obj":"2_test"}]},{"project":"0_colil","denotations":[{"id":"31316328-16364899-631192","span":{"begin":230,"end":234},"obj":"16364899"},{"id":"31316328-18039974-631193","span":{"begin":250,"end":254},"obj":"18039974"},{"id":"31316328-16677822-631194","span":{"begin":402,"end":406},"obj":"16677822"},{"id":"31316328-24918638-631195","span":{"begin":651,"end":655},"obj":"24918638"},{"id":"31316328-26921371-631196","span":{"begin":745,"end":749},"obj":"26921371"},{"id":"31316328-29449528-631197","span":{"begin":766,"end":770},"obj":"29449528"},{"id":"31316328-12376549-631198","span":{"begin":893,"end":897},"obj":"12376549"},{"id":"31316328-19020035-631199","span":{"begin":915,"end":919},"obj":"19020035"},{"id":"31316328-20133938-631200","span":{"begin":935,"end":939},"obj":"20133938"},{"id":"31316328-27143756-631201","span":{"begin":956,"end":960},"obj":"27143756"},{"id":"31316328-24776795-631202","span":{"begin":1004,"end":1008},"obj":"24776795"},{"id":"31316328-29449528-631203","span":{"begin":1025,"end":1029},"obj":"29449528"},{"id":"31316328-29449528-631204","span":{"begin":1146,"end":1150},"obj":"29449528"},{"id":"31316328-18455991-631205","span":{"begin":1304,"end":1308},"obj":"18455991"},{"id":"31316328-24776795-631206","span":{"begin":1327,"end":1331},"obj":"24776795"},{"id":"31316328-15668976-631207","span":{"begin":1710,"end":1714},"obj":"15668976"},{"id":"31316328-22922411-631208","span":{"begin":1971,"end":1975},"obj":"22922411"},{"id":"31316328-22922411-631209","span":{"begin":2202,"end":2206},"obj":"22922411"}],"attributes":[{"subj":"31316328-16364899-631192","pred":"source","obj":"0_colil"},{"subj":"31316328-18039974-631193","pred":"source","obj":"0_colil"},{"subj":"31316328-16677822-631194","pred":"source","obj":"0_colil"},{"subj":"31316328-24918638-631195","pred":"source","obj":"0_colil"},{"subj":"31316328-26921371-631196","pred":"source","obj":"0_colil"},{"subj":"31316328-29449528-631197","pred":"source","obj":"0_colil"},{"subj":"31316328-12376549-631198","pred":"source","obj":"0_colil"},{"subj":"31316328-19020035-631199","pred":"source","obj":"0_colil"},{"subj":"31316328-20133938-631200","pred":"source","obj":"0_colil"},{"subj":"31316328-27143756-631201","pred":"source","obj":"0_colil"},{"subj":"31316328-24776795-631202","pred":"source","obj":"0_colil"},{"subj":"31316328-29449528-631203","pred":"source","obj":"0_colil"},{"subj":"31316328-29449528-631204","pred":"source","obj":"0_colil"},{"subj":"31316328-18455991-631205","pred":"source","obj":"0_colil"},{"subj":"31316328-24776795-631206","pred":"source","obj":"0_colil"},{"subj":"31316328-15668976-631207","pred":"source","obj":"0_colil"},{"subj":"31316328-22922411-631208","pred":"source","obj":"0_colil"},{"subj":"31316328-22922411-631209","pred":"source","obj":"0_colil"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#93ec97","default":true},{"id":"0_colil","color":"#ec93a8"}]}]}}