PMC:6610326 / 92703-93824 JSONTXT

{"project":"2_test","denotations":[{"id":"31316328-23578819-38515894","span":{"begin":140,"end":144},"obj":"23578819"},{"id":"31316328-17929040-38515895","span":{"begin":477,"end":481},"obj":"17929040"},{"id":"31316328-17725983-38515896","span":{"begin":579,"end":583},"obj":"17725983"},{"id":"31316328-19344250-38515897","span":{"begin":609,"end":613},"obj":"19344250"},{"id":"31316328-21059924-38515898","span":{"begin":632,"end":636},"obj":"21059924"},{"id":"31316328-24154542-38515899","span":{"begin":654,"end":658},"obj":"24154542"},{"id":"31316328-24154542-38515900","span":{"begin":693,"end":697},"obj":"24154542"},{"id":"31316328-24704492-38515901","span":{"begin":835,"end":839},"obj":"24704492"},{"id":"31316328-23827948-38515902","span":{"begin":973,"end":977},"obj":"23827948"}],"text":"In vulnerable MNs lacking Ca2+-binding proteins calbindin and parvalbumin, Ca2+ is largely taken up by mitochondria (Lautenschläger et al., 2013). As a result, extensive mitochondrial transport to the dendritic space is required to maintain Ca2+ homeostasis. The normal distribution of mitochondria is also perturbed in ALS patient MNs. Whereas they are depleted in distal dendrites and axons, mitochondria also accumulate in the soma and proximal axon hillock (Sasaki et al., 2007). Disturbed mitochondrial dynamics were also described in MNs in mutant SOD1G93A (De Vos et al., 2007; Sotelo-Silveira et al., 2009; Bilsland et al., 2010; Magrané et al., 2014) and TDP-43A315T (Magrané et al., 2014) mice. In addition, iPSC-derived A4V MNs exhibit disturbances in mitochondrial morphology and motility within the axon (Kiskinis et al., 2014). Similarly, expression of mutant TDP-43 in spinal cord primary neurons leads to abnormal distribution of mitochondria (Wang et al., 2013). Dysfunctional Ca2+ uptake by mitochondria may therefore result in elevated intracellular Ca2+ levels, thus contributing to neurodegeneration."}

{"project":"0_colil","denotations":[{"id":"31316328-23578819-631351","span":{"begin":140,"end":144},"obj":"23578819"},{"id":"31316328-17929040-631352","span":{"begin":477,"end":481},"obj":"17929040"},{"id":"31316328-17725983-631353","span":{"begin":579,"end":583},"obj":"17725983"},{"id":"31316328-19344250-631354","span":{"begin":609,"end":613},"obj":"19344250"},{"id":"31316328-21059924-631355","span":{"begin":632,"end":636},"obj":"21059924"},{"id":"31316328-24154542-631356","span":{"begin":654,"end":658},"obj":"24154542"},{"id":"31316328-24154542-631357","span":{"begin":693,"end":697},"obj":"24154542"},{"id":"31316328-24704492-631358","span":{"begin":835,"end":839},"obj":"24704492"},{"id":"31316328-23827948-631359","span":{"begin":973,"end":977},"obj":"23827948"}],"text":"In vulnerable MNs lacking Ca2+-binding proteins calbindin and parvalbumin, Ca2+ is largely taken up by mitochondria (Lautenschläger et al., 2013). As a result, extensive mitochondrial transport to the dendritic space is required to maintain Ca2+ homeostasis. The normal distribution of mitochondria is also perturbed in ALS patient MNs. Whereas they are depleted in distal dendrites and axons, mitochondria also accumulate in the soma and proximal axon hillock (Sasaki et al., 2007). Disturbed mitochondrial dynamics were also described in MNs in mutant SOD1G93A (De Vos et al., 2007; Sotelo-Silveira et al., 2009; Bilsland et al., 2010; Magrané et al., 2014) and TDP-43A315T (Magrané et al., 2014) mice. In addition, iPSC-derived A4V MNs exhibit disturbances in mitochondrial morphology and motility within the axon (Kiskinis et al., 2014). Similarly, expression of mutant TDP-43 in spinal cord primary neurons leads to abnormal distribution of mitochondria (Wang et al., 2013). Dysfunctional Ca2+ uptake by mitochondria may therefore result in elevated intracellular Ca2+ levels, thus contributing to neurodegeneration."}