**Tiny microRNAs Fine-Tune Amyotrophic Lateral Sclerosis Regulation**

Utpal Bhadra, Anisha Pal, Jagamohan Chhatai and Manika Pal Bhadra

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/63528

#### **Abstract**

[87] Morel L, Regan M, Higashimori H, Ng SK, Esau C, Vidensky S, Rothstein J, Yang Y. Neuronal exosomal miRNA-dependent translational regulation of astroglial glutamate

[88] Ilieva H, Polymenidou M, Cleveland DW. Non-cell autonomous toxicity in neurode‐

[89] Boillee S, Vande Velde C, Cleveland DW. ALS: a disease of motor neurons and their

[90] Lobsiger CS, Boillee S, McAlonis-Downes M, Khan AM, Feltri ML, Yamanaka K, Cleveland DW. Schwann cells expressing dismutase active mutant SOD1 unexpectedly slow disease progression in ALS mice. Proc. Natl. Acad. Sci. U. S. A. 2009;106(11):4465–

[91] Chen K, Northington FJ, Martin LJ. Inducible nitric oxide synthase is present in motor neuron mitochondria and Schwann cells and contributes to disease mechanisms in ALS

[92] Parisi C, Arisi I, D'Ambrosi N, Storti AE, Brandi R, D'Onofrio M, Volonté C. Dysregu‐ lated microRNAs in amyotrophic lateral sclerosis microglia modulate genes linked to

[93] Poloni M, Facchetti D, Mai R, Micheli A, Agnoletti L, Francolini G, Mora G, Camana C, Mazzini L, Bachetti T. Circulating levels of tumour necrosis factor-alpha and its soluble receptors are increased in the blood of patients with amyotrophic lateral sclerosis.

[94] Hensley K, Fedynyshyn J, Ferrell S, Floyd RA, Gordon B, Grammas P, Hamdheydari L, Mhatre M, Mou S, Pye QN, Stewart C, West M, West S, Williamson KS. Message and protein-level elevation of tumor necrosis factor alpha (TNF alpha) and TNF alphamodulating cytokines in spinal cords of the G93A-SOD1 mouse model for amyotrophic

[95] D'Ambrosi N, Finocchi P, Apolloni S, Cozzolino M, Ferri A, Padovano V, Pietrini G, Carrì MT, Volonté C. The proinflammatory action of microglial P2 receptors is en‐ hanced in SOD1 models for amyotrophic lateral sclerosis. J. Immunol. 2009;183(7):4648–

generative disorders: ALS and beyond. J. Cell Biol. 2009;187(6):761–772

transporter GLT1. J. Biol. Chem. 2013;288(10):7105–7116.

nonneuronal neighbors. Neuron. 2006;52(1):39–59.

mice. Brain Struct. Funct. 2010;214(2–3):219–234.

neuroinflammation. Cell Death Dis. 2013;4:e959.

lateral sclerosis. Neurobiol. Dis. 2003;14(1):74–80.

Neurosci. Lett. 2000;287(3):211–214.

4470.

134 Update on Amyotrophic Lateral Sclerosis

4656.

Progressing muscle wasting and dramatic neurodegeneration of upper and lower motor neurons are the initial symptoms of amyotrophic lateral sclerosis (ALS) that eventually cause aetiology or death in quick succession. The functional mechanism of ALS is non-cell autonomous but it strongly influences on non-neural cells including microglia, astrocyte muscles and T cell. In ALS, neurodegeneration is triggered by at least four gene mutations that are not related to any classical signalling pathways, molecular mechanism or known cellular ingredients. MicroRNA is endogenous tiny non-coding RNA, which is required for fine-tuning or micromanaging protein expression post-transcriptionally. In this review, we identified numerous microRNAs and their possible targets in ALS-related genes. These microRNAs misprocess ALSrelated protein-coding genes via microRNA-gene circuits. This result sheds a strong link between microRNA and ALS genes. The mechanistic insight of multiple microRNAs related to ALS is required to treat neuro-inflammation and neurodegradation. It is proposed that the micro-regulation of multiple microRNAs is involved in generation of unique neuroprotective agent against ALS. Therefore, a classical and novel microRNA-mediated therapy might unravel an alternative strategy for ALS-related neurodegeneration. This strategy indeed implicates real promises to illustrate a unique impact for ALS cure.

**Keywords:** amyotrophic lateral sclerosis (ALS), small microRNA, hotspot, microRNAmediated therapy, neurodegeneration

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
