Role of Apoptosis in Neurodegeneration: Therapeutic Targets and Strategies

Neurodegeneration, characterized by the progressive loss of structure and function of neurons, poses a significant challenge to healthcare. A fundamental aspect of neurodegeneration is the dysregulation of apoptosis, the programmed cell death mechanism crucial for maintaining tissue homeostasis. Dysfunctional apoptotic pathways can lead to the untimely death of neurons, contributing to the pathogenesis of disorders such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis (ALS). Apoptosis is initiated through various signaling pathways, including the intrinsic (mitochondrial) and extrinsic (death receptor) pathways. In neurodegenerative diseases, these pathways can become activated due to various factors, such as protein misfolding, oxidative stress, DNA damage, inflammation, neuroinflammatory feedback loop, mitochondrial dysfunction, loss of neurotrophic factors, and genetic mutations. All these mechanisms stand as potential therapeutic targets in apoptosis-induced neurodegeneration and altering these targets like enhancing the activity of antiapoptotic factors like Bcl-2 and Bcl-XL, modulating specific genes involved, promoting neurotrophic factors, maintaining healthy mitochondria, and reducing neuroinflammation and target protein clearance mechanisms by using different strategies like gene therapy, small molecule inhibitors, stem cell therapies, and immunomodulation either individually or by combining these approaches stand as a valuable strategy against it. This chapter will also briefly explore the potential of natural bioactive compounds and other active medicinal compounds as interventional agents targeting therapeutic pathways associated with apoptosis and neurodegeneration.