**2. Symptoms of ALS**

**1. Overview and introduction**

136 Update on Amyotrophic Lateral Sclerosis

phy.com/people/lou-gehrig-9308266).

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‐

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]).

"ALS is like a lit candle: it melts your nerves and leaves your body a pile of wax. Often, it begins with the legs and works its way up. You lose control of your thigh muscles, so that you cannot support yourself standing. You lose control of your trunk muscles, so that you cannot sit up straight. By the end, if you are still alive, you are breathing through a tube in a hole in your throat, while your soul, perfectly awake, is imprisoned inside a limp husk, perhaps able to blink, or cluck a tongue, like something from a science fiction movie, the man frozen inside his own flesh. This takes no more than 5 years from the day you contract the disease". Courtesy from "Tuesdays with Morrie" by Mitch Albom.

Each individual patient may experience symptoms differently. Symptoms may include:


As the disease progresses, symptoms may comprise:

