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The multifaceted role of glial cells in amyotrophic lateral sclerosis

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Abstract

Despite indisputable progress in the molecular and genetic aspects of amyotrophic lateral sclerosis (ALS), a mechanistic comprehension of the neurodegenerative processes typical of this disorder is still missing and no effective cures to halt the progression of this pathology have yet been developed. Therefore, it seems that a substantial improvement of the outcome of ALS treatments may depend on a better understanding of the molecular mechanisms underlying neuronal pathology and survival as well as on the establishment of novel etiological therapeutic strategies. Noteworthy, a convergence of recent data from multiple studies suggests that, in cellular and animal models of ALS, a complex pathological interplay subsists between motor neurons and their non-neuronal neighbours, particularly glial cells. These observations not only have drawn attention to the physiopathological changes glial cells undergo during ALS progression, but they have moved the focus of the investigations from intrinsic defects and weakening of motor neurons to glia–neuron interactions. In this review, we summarize the growing body of evidence supporting the concept that different glial populations are critically involved in the dreadful chain of events leading to motor neuron sufferance and death in various forms of ALS. The outlined observations strongly suggest that glial cells can be the targets for novel therapeutic interventions in ALS.

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Acknowledgments

Chiara F. Valori receives a stipend from the Swiss National Science Foundation (Grant 31003A-132864). Daniela Rossi received funds from the Telethon Foundation (Grant GGP05244) to study the role of glial cells in ALS pathogenesis and progression. Figures were produced using Servier Medical Art (http://www.servier.com).

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Authors and Affiliations

  1. Department of Neuropathology, German Center for Neurodegenerative Diseases (DZNE), Paul-Ehrlich-Strasse 17, 72076, Tübingen, Germany

    Chiara F. Valori

  2. Laboratory for Research on Neurodegenerative Disorders, IRCCS Fondazione Salvatore Maugeri, Via Maugeri 10, 27100, Pavia, Italy

    Liliana Brambilla, Francesca Martorana & Daniela Rossi

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  1. Chiara F. Valori
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  2. Liliana Brambilla
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Correspondence to Daniela Rossi.

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Valori, C.F., Brambilla, L., Martorana, F. et al. The multifaceted role of glial cells in amyotrophic lateral sclerosis. Cell. Mol. Life Sci. 71, 287–297 (2014). https://doi.org/10.1007/s00018-013-1429-7

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