**1. Overview and introduction**

Amyotrophic lateral sclerosis (ALS) is an important neuromuscular disease [1]. ALS was recognized back in 1850 by the English neurophysiologist Augustus Waller for the appearance of shrivelled nerve fibres. In 1869, in a scientific literature it was described and named ALS by the French neurologist Jean-Martin Charcot [2]. ALS, otherwise known as Lou Gehrig's disease, caused a baseball player, Lou Gehrig, to retire from his peak season. This New York Yankees player was called the iron horse for his contribution in the field (adapted from http://www.hopkinsmedicine.org/neurology\_neurosurgery/ centers\_clinics/als/conditions/als\_amyotrophic\_lateral\_sclerosis.html, http://www.biogra‐ phy.com/people/lou-gehrig-9308266).

Gradual degeneration of motor neurons in the brain and spinal cord is sought after to char‐ acterize this disease [1]. After the disease contracts, the motor neurons can no longer deliver impulses to the muscles, resulting in atrophy of muscles and muscle weakness (**Figure 1**). ALS does not disrupt a person's intellectual reasoning, vision, hearing or sense of taste, smell and touch. Mostly, ALS does not affect a person's bowel, sexual or bladder functions. ALS is often referred to as a neurodegenerative syndrome because the disease becomes evident in various

**Figure 1.** Under normal physiological condition, pri-miRNAs are processed in nucleus by Drosha along with its part‐ ner DGCR8. Recently it has been revealed that interactions with TDP-43 and FUS–TLS enhance miRNA biogenesis. In this diagram the pri-miRNAs, regulated by TDP-43, have been shown in blue colour, and the pri-miRNAs, regulated by FUS–TLS, have been shown in red colour. It has also been demonstrated that TDP43 associates with Dicer complex and helps in the processing of pre-miR-143 and pre-miR-574 into mature miRNAs in cytoplasm (adapted from Bicker S, Schratt G. MicroRNAs in ALS: small pieces to the puzzle. EMBO J. 2015;34[3]:2601–3 and Ref. [21]).

patterns. ALS occurs scarcely and spontaneously. Currently, there is no straightforward and classical cure for ALS (adapted from http://www.hopkinsmedicine.org/neurology\_neurosur‐ gery/centers\_clinics/als/conditions/als\_amyotrophic\_lateral\_sclerosis.html, http://emedi‐ cine.medscape.com/article/1170097-clinical).

MicroRNAs are the tiny endogenous non-coding RNA that represses protein synthesis posttranscriptionally by coupling at the 3′ untranslated leader sequences of target mRNAs [4]. MicroRNA micro-manages a broad range of biological process including developmental decisions, cellular differentiation, programmed cell death for pattern formation, and many pivotal roles in different human diseases [5]. At least 500–1000 microRNAs are found in vertebrate [6]. However, each microRNA can target numerous mRNAs [7]. It is suggested that 30–40% of human transcriptome is under control of different miRNA-gene circuits.

Biogenesis, processing and functional mechanism of microRNA are unique. Four different functional processes are involved in microRNA-mediated gene expression where (1) cotranslational protein synthesis is disrupted, (2) translation elongation is inhibited, (3) transla‐ tion product is terminated prematurely and finally (4) translation initiation is disrupted. MicroRNA inhibits their functional targets by sequestering to target mRNAs [8].

Basically, microRNA can be used as a fine-tuner for different gene regulatory networks. Especially numerous microRNAs are expressed in different sites of the brains [9]. They participate in the functional mechanism of brain development. They have important roles in brain morphogenesis, neuronal differentiation, dendrite and spine developments, synaptic structure formation and neuronal plasticity, etc. [10]. Multiple clusters of microRNA play important parts in different acute and chronic pathological disorders in the brain. In this review we have mentioned a set of microRNA that produce a distinct cluster in different ALS-related genes. The dysregulation of these microRNAs collectively misregulates multiple mRNAs related to ALS and other neurological diseases. Multiple microRNAs can simultaneously control several endogenous mRNAs because 3′ UTR of an mRNA can have complementary sites for a cluster of microRNAs; conversely a single microRNA can regulate multiple mRNAs [11]. In protein homeostasis, different cellular events participate with different microRNAs. However, different microRNAs may involve various mediators to control gene expression [12].
