**2. Role of Cell Death in the Onset of Neurodegeneration**

Neurological disorders are mainly characterized by increased degradation in the functioning of neurons due to the destruction of synapses and axons, eventually leading to nerve cell death. An understanding of the mechanism that leads to the homeostasis of cellular elements and neurodegradation is highly important for developing novel therapeutic treatments for the diseases [15–19]. The healthy cells in the human body transform to preserve the normal homeostasis of tissues; however, post-mitotic neurons harbor very little capacity to regenerate and their survival is essential to ensure the proper functioning of the nervous system [20]. The death of neurons promotes the development of nervous system; however, if occurring in excess, it leads to declined functioning of nervous system and causes the progression of neurodegenerative diseases, which can be indicated by a

range of acute insults, from stroke and traumatic brain injury (TBI) to enduring critical conditions such as Parkinson's disease [21], Alzheimer's disease [22], and amyotrophic lateral sclerosis [23].

Several studies have been conducted to understand the neuropathology behind the chronic conditions of these diseases, and stereotypical patterns of neurodegeneration have been identified in different regions of the central nervous system, which correspond to the disease severity clinically [24]. Several other pathological pathways, such as impairment in axonal transport and synaptic function, oxidative stress, dysfunction of lysosomes and mitochondria [25,26], activation of microglial cells and protein aggregation, also contribute to neuronal damage [27]. Other factors such as genetics, age, and environmental factors influence the disruption of neuronal homeostasis and aggravate the existing neurodegeneration by activating the signaling of different molecules, ultimately causing cell death and declined functioning of the nervous system [28].

With the advancement of technology in recent years, the understanding of pathology and genetic changes invoked in neurodegenerative diseases has significantly improved but is still unsatisfying. Due to complex biology, the connection between the origin and execution of the death of neurons is still lucid [2]. The pathway involved in cell death and the mechanism responsible for its activation is still under question, and unraveling it is important to drive the development of new target-oriented therapeutic medications. There are several pathways that regulate the cell death of neurons, which are explained below.
