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Neurotrophic Therapy for ALS/MND

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Handbook of Neurotoxicity

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Abstract

Neurotrophic factors have a large range of activities in the nervous system that consist of functions in development, plasticity, neurogenesis, disease, and injury. In the context of amyotrophic lateral sclerosis (ALS), it has long been hypothesized that lack of neurotrophic growth factors is one of the neurotoxic contributors to the disease that results in death of motor neurons. This has led to a considerable number of clinical trials undertaken involving neurotrophic therapy for ALS, although none have shown benefit. This chapter will review the cause and pathology of ALS and how neurotrophic factors relate to neurotoxicity in this disease. The treatments targeted at neurotoxicity and results of trials will be discussed, in particular neurotrophic factors. This will include glial cell-derived neurotrophic factor (GDNF), brain-derived growth factor (BDNF), neurotrophin-3 (NT-3), ciliary neurotrophic factor (CNTF), insulin-like growth factor (IGF), vascular endothelial cell growth factor (VEGF), fibroblast growth factor (FGF), and hepatocyte growth factor (HGF). Also highlighted is the potential for reexamining neurotrophic factors as treatments for ALS, including new delivery methods.

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Abbreviations

ALS:

Amyotrophic lateral sclerosis

BBB:

Blood–brain barrier

BDNF:

Brain-derived growth factor

C9ORF72:

Chromosome 9 open reading frame 72

CNS:

Central nervous system

CNTF:

Ciliary neurotrophic factor

FGF:

Fibroblast growth factor

GDNF:

Glial cell-derived neurotrophic factor

HGF:

Hepatocyte growth factor

IGF:

Insulin-like growth factor

NGF:

Nerve growth factor

NMJ:

Neuromuscular junction

NT-3:

Neurotrophin-3

NT-4:

Neurotrophin-4

NT-5:

Neurotrophin-5

SOD1:

Superoxide dismutase 1

SOD1G93A:

Mutated SOD1 glycine to alanine position 93

TDP-43:

Transactivation response DNA-binding protein of 43 kDa

TUDCA:

Tauroursodeoxycholic acid

VEGF:

Vascular endothelial cell growth factor

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Acknowledgments

Funding from the Motor Neuron Disease Research Institute of Australia supported this work.

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Authors and Affiliations

  1. College of Medicine & Public Health, Flinders Health & Medical Research Institute, Flinders University, Adelaide, SA, Australia

    Megan Dubowsky, Stephanie R Shepheard & Mary-Louise Rogers

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  1. Megan Dubowsky
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  2. Stephanie R Shepheard
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  3. Mary-Louise Rogers
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Correspondence to Mary-Louise Rogers .

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  1. Department of Biomedical Sciences, East Tennessee State University, Johnson City, TN, USA

    Richard M. Kostrzewa

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Dubowsky, M., Shepheard, S.R., Rogers, ML. (2022). Neurotrophic Therapy for ALS/MND. In: Kostrzewa, R.M. (eds) Handbook of Neurotoxicity. Springer, Cham. https://doi.org/10.1007/978-3-030-71519-9_34-1

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  • DOI: https://doi.org/10.1007/978-3-030-71519-9_34-1

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