BB-rel@ldeleger:BB-rel-20005916 / 99-2262 JSONTXT

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bionlp-ost-19-BB-rel-train

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Id Subject Object Predicate Lexical cue
T2 0-2163 Paragraph denotes Multiple signaling pathways play key regulatory roles during the development of peripheral nervous system (PNS) and also in neuroregeneration process following nerve degeneration. Schwann cells, the glial cells of the PNS, by interacting with neuronal (axonal) ligands, mainly neuregulins via receptor tyrosine kinase (RTK) complex, ErbB2/ErbB3, initiate intracellular signaling pathways to drive proliferation and differentiation of Schwann cells, both during development and the process of regeneration and re-myelination after nerve injury. One of the major signaling kinases, extracellular signal-regulated kinase-1/2 (ERK1/2), that is also a downstream signaling pathway of neuregulin-ErbB2/ErbB3 activation, has been identified as a key regulator of Schwann cell proliferation, differentiation, demyelination and nerve regeneration. Recent studies have provided evidence that the bacterium that causes human leprosy, Mycobacterium leprae that has a unique capacity to invade Schwann cells of the adult PNS, utilizes the neuregulin-ErbB2/ErbB3 associated signaling network to the bacterial advantage. M. leprae directly bind to ErbB2 on myelinated Schwann cells and activate the RTK by a novel route that bypasses the classical neuregulin/growth factor-induced ErbB2-ErbB3 heterodimerization, and subsequently induce downstream the canonical Erk1/2 signaling, leading to myelin breakdown and subsequent axonal damage. This initial injury provides a survival advantage for M. leprae as it induces de-differentiation and generates myelin-free cells, which are highly susceptible to M. leprae invasion and promote bacterial survival. Once invaded M. leprae activate Erk1/2 via a non-canonical pathway and subsequently increase the cell proliferation and maintain the infected cells in de-differentiated state, thereby preventing remyelination. Therefore, by subverting major RTKs and signaling pathways in adult Schwann cells M. leprae appear to propagate the bacterial niche and maintain survival within the PNS. These studies may also provide new insights into our understanding of signaling mechanisms involve in both neurodegeneration and neuroregeneration.
T4 80-105 Habitat denotes peripheral nervous system
T5 107-110 Habitat denotes PNS
T6 160-165 Habitat denotes nerve
T7 180-193 Habitat denotes Schwann cells
T8 199-221 Habitat denotes glial cells of the PNS
T9 218-221 Habitat denotes PNS
T10 434-447 Habitat denotes Schwann cells
T12 530-542 Habitat denotes nerve injury
T11 530-535 Habitat denotes nerve
T13 756-768 Habitat denotes Schwann cell
T14 819-824 Habitat denotes nerve
T15 908-913 Habitat denotes human
T16 923-943 Microorganism denotes Mycobacterium leprae
T17 981-1011 Habitat denotes Schwann cells of the adult PNS
T19 1002-1011 Habitat denotes adult PNS
T18 1002-1007 Habitat denotes adult
T20 1106-1115 Microorganism denotes M. leprae
T21 1142-1166 Habitat denotes myelinated Schwann cells
T22 1436-1442 Habitat denotes injury
T23 1477-1486 Microorganism denotes M. leprae
T24 1534-1551 Habitat denotes myelin-free cells
T25 1585-1594 Microorganism denotes M. leprae
T26 1649-1658 Microorganism denotes M. leprae
T27 1733-1737 Habitat denotes cell
T28 1769-1783 Habitat denotes infected cells
T30 1908-1927 Habitat denotes adult Schwann cells
T29 1908-1913 Habitat denotes adult
T31 1928-1937 Microorganism denotes M. leprae
T32 2011-2014 Habitat denotes PNS
E1 923-943 Lives_In denotes Mycobacterium leprae
E2 923-943 Lives_In denotes Mycobacterium leprae
E3 923-943 Lives_In denotes Mycobacterium leprae
E4 923-943 Lives_In denotes Mycobacterium leprae
E5 1106-1115 Lives_In denotes M. leprae
E6 1585-1594 Lives_In denotes M. leprae
E7 1649-1658 Lives_In denotes M. leprae
E8 1649-1658 Lives_In denotes M. leprae
E9 1928-1937 Lives_In denotes M. leprae
E10 1928-1937 Lives_In denotes M. leprae
R1 E1 T16 Microorganism Mycobacterium leprae,Mycobacterium leprae
R2 E1 T17 Location Mycobacterium leprae,Schwann cells of the adult PNS
R3 E2 T16 Microorganism Mycobacterium leprae,Mycobacterium leprae
R4 E2 T19 Location Mycobacterium leprae,adult PNS
R5 E3 T16 Microorganism Mycobacterium leprae,Mycobacterium leprae
R6 E3 T18 Location Mycobacterium leprae,adult
R7 E4 T16 Microorganism Mycobacterium leprae,Mycobacterium leprae
R8 E4 T15 Location Mycobacterium leprae,human
R9 E5 T20 Microorganism M. leprae,M. leprae
R10 E5 T21 Location M. leprae,myelinated Schwann cells
R11 E6 T25 Microorganism M. leprae,M. leprae
R12 E6 T24 Location M. leprae,myelin-free cells
R13 E7 T26 Microorganism M. leprae,M. leprae
R14 E7 T28 Location M. leprae,infected cells
R15 E8 T26 Microorganism M. leprae,M. leprae
R16 E8 T27 Location M. leprae,cell
R17 E9 T31 Microorganism M. leprae,M. leprae
R18 E9 T32 Location M. leprae,PNS
R19 E10 T31 Microorganism M. leprae,M. leprae
R20 E10 T30 Location M. leprae,adult Schwann cells