Calcium binding proteins in selective vulnerability of motor neurons

László Siklós, Stanley H. Appel

Research output: Chapter in Book/Report/Conference proceedingChapter

3 Citations (Scopus)

Abstract

Introduction Since the mid-1990s, the specific etiologies and mechanisms leading to dysfunction and loss of motor neurons in ALS have been under intensive investigation. No single mechanism appears to explain the devastating and inexorable injury to motor neurons. What appears far more likely is a convergence of a number of different mechanisms that collectively or sequentially impair motor neuron structure and function. Among the various proposals implicated, increased free radicals and oxidative stress, increased glutamate excitotoxicity, increased cellular aggregates and increased intracellular calcium have received the most attention (Rothstein, 1995; Cleveland, 1999; Shaw & Eggett, 2000; Rowland, 2000; Julien, 2001; Rowland & Shneider, 2001; Cleveland & Rothstein, 2001). None of these mechanisms is mutually exclusive and altered calcium homeostasis, free radicals, and glutamate excitotoxicity may all participate in the cell injury cascade leading to motor neuron death. Alterations in one parameter can lead to alterations in other parameters, and each can enhance and propagate the injury cascade. Such perturbations could critically impair motor neuron mitochondria and neurofilaments, compromise energy production and axoplasmic flow, and impair synaptic function. However, these alterations would be expected to adversely affect most neurons, and the critical question is why motor neurons are uniquely sensitive to injury in ALS, and why some motor neurons are relatively resistant to injury. Our own hypothesis focuses on the critical role of intracellular calcium and the inability of vulnerable motor neurons to handle an increased intracellular calcium load, possibly related to the relative paucity of the calcium binding proteins, calbindin D28k and parvalbumin.

Original languageEnglish
Title of host publicationNeurodegenerative Diseases: Neurobiology, Pathogenesis and Therapeutics
PublisherCambridge University Press
Pages65-79
Number of pages15
ISBN (Print)9780511544873, 052181166X, 9780521811668
DOIs
Publication statusPublished - Jan 1 2005

Fingerprint

Calcium-Binding Proteins
Motor Neurons
Wounds and Injuries
Calcium
Free Radicals
Glutamic Acid
Calbindin 1
Parvalbumins
Axonal Transport
Intermediate Filaments
Mitochondria
Oxidative Stress
Homeostasis
Neurons

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Siklós, L., & Appel, S. H. (2005). Calcium binding proteins in selective vulnerability of motor neurons. In Neurodegenerative Diseases: Neurobiology, Pathogenesis and Therapeutics (pp. 65-79). Cambridge University Press. https://doi.org/10.1017/CBO9780511544873.007

Calcium binding proteins in selective vulnerability of motor neurons. / Siklós, László; Appel, Stanley H.

Neurodegenerative Diseases: Neurobiology, Pathogenesis and Therapeutics. Cambridge University Press, 2005. p. 65-79.

Research output: Chapter in Book/Report/Conference proceedingChapter

Siklós, L & Appel, SH 2005, Calcium binding proteins in selective vulnerability of motor neurons. in Neurodegenerative Diseases: Neurobiology, Pathogenesis and Therapeutics. Cambridge University Press, pp. 65-79. https://doi.org/10.1017/CBO9780511544873.007
Siklós L, Appel SH. Calcium binding proteins in selective vulnerability of motor neurons. In Neurodegenerative Diseases: Neurobiology, Pathogenesis and Therapeutics. Cambridge University Press. 2005. p. 65-79 https://doi.org/10.1017/CBO9780511544873.007
Siklós, László ; Appel, Stanley H. / Calcium binding proteins in selective vulnerability of motor neurons. Neurodegenerative Diseases: Neurobiology, Pathogenesis and Therapeutics. Cambridge University Press, 2005. pp. 65-79
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