**Abstract**

Muscles are the enriched reservoir of proteins in the body. During any workout or exercise, the demand in the form of energy is essentially required by the muscle. Energy expenditure of skeletal muscle is more dependent on the type of demand. There is particular homeostasis within the body that avoid surplus energy expenditure and this prevents any muscle loss. Muscle atrophy is termed as the loss of skeletal muscle mass due to immobility, malnutrition, medications, aging, cancer cachexia, variety of injuries or diseases that impact the musculoskeletal or nervous system. Hence, atrophy within the skeletal muscle initiates further cause fatigue, pain, muscle weakness, and disability in human subjects. Therefore, starvation and reduced muscle mass further initiate numerous signaling pathways including inflammatory, antioxidant signaling, mitochondria bio-energetic failure, AMPactivated protein kinase (AMPK), Sirtuin 1(SIRT1), BDNF/TrkB/PKC, Autophagy, ubiquitin-proteasome systems, etc. Here, in this chapter, we will mention molecular mechanisms involved in therapeutic targets and available Pharmacological Interventions with the latest updates.

**Keywords:** molecular mechanisms, therapeutic targets, pharmacological Interventions

#### **1. Introduction**

Muscles are enormous protein reservoirs within the body. It is a profound source of various amino acids required for energy production used by various organs (such as brain, liver, heart) during energy demand and disease conditions (cancer, AIDS, burn, heart failure). However, extensive protein requirement does not consider good in case of cachexia which might lead to increased morbidity and mortality. Skeletal muscle is an organ with plastic characteristics and regulated by several signaling pathways that control cell and protein turnover. The skeletal muscle atrophy may be due to lower muscle mass, disease. However, disuse muscle mediated acute atrophy is reversed through exercise. Furthermore, chronic atrophy such as sarcopenia features as loss of muscle mass strength with age. Moreover, other chronic diseases such as diabetes or disease of muscles (muscle dystrophy) cause

nerve damage to innervate to the muscle [1]. In muscle atrophy, a proteolytic system gets activated while contractile proteins and organelles are removed results in the shrinkage of muscle fibers.

Spinal muscular atrophy (SMA), a kind of intense neuromuscular disease depicts as chief genetic cause of death in infants. It is featured as alpha motor neuron degeneration within the anterior horn region of the spinal cord and brain stem that is the leading cause of progressive muscle weakness. SMA is inherited as autosomal recessive disorder and the most common form (95% cases) caused by certain mutations in the survival motor neuron 1 (*SMN1, SMN*<sup>T</sup> ) gene localized on chromosome 5q12.2. The genetic deletion or carries a mutation of the SMN1 gene resulting SMN protein deficit. On the other hand, the SMN2 gene develops a relatively small amount of functional SMN protein and SMN2 copy numbers further determine the severity of the disease. The incidence of SMA is approx. 1 in 10,000 live births while prevalence estimates 1–2 in 100,000 affected individuals with extremely shortened life expectancy. SMA characterizes in various forms depending on the age of inception such as Infants being severely hypotonic possess feeding problems, further reach growing age of children does found with difficulty climbing stairs proceeded with frequent falls. The clinical manifestation of SMA is usually heterogeneous and scored to a range from severe to mild phenotype which is further divided into mainly 3 subtypes as Type I (also known as Werdnig-Hoffmann disease), type II and, type III (also called Kugelberg Welander disease). SMA categorized as type 0, a serious and rigorous form, lower/absent movements, abnormal muscle contractions, and immediate need for ventilation support. SMA type IV, a mild late (adult) onset [2]. Hence, improve understanding regarding the molecular pathogenesis mechanisms cause for muscle atrophy or muscle wasting attribute the efforts to designate the safe and effective therapy for affected human subjects.
