title: Ca2+, mitochondria and selective motoneuron vulnerability: implications for ALS.
abstract: Motoneurons are selectively damaged in amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. Although the underlying mechanisms are not completely understood, increasing evidence indicates that motoneurons are particularly sensitive to disruption of mitochondria and Ca(2+)-dependent signalling cascades. Comparison of ALS-vulnerable and ALS-resistant neurons identified low Ca(2+)-buffering capacity and a strong impact of mitochondrial signal cascades as important risk factors. Under physiological conditions, weak Ca(2+) buffers are valuable because they facilitate rapid relaxation times of Ca(2+) transients in motoneurons during high-frequency rhythmic activity. However, under pathological conditions, weak Ca(2+) buffers are potentially dangerous because they accelerate a vicious circle of mitochondrial disruption, Ca(2+) disregulation and excitotoxic cell damage.
authors: Zentrum Physiologie, Georg-August Universität Göttingen, Humboldtallee 23, 37073 Göttingen, Germany.
authors: Friederike
authors: F
authors: von Lewinski
authors: Bernhard U
authors: BU
authors: Keller
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology*; D008959:Models, Neurological; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology*; D017382:Reactive Oxygen Species; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology
chemical_list: D017382:Reactive Oxygen Species; D002118:Calcium