Senotherapeutics in Neurological Disorders

Neurological disorders primarily are an outcome of neurodegeneration, which is an age-associated progressive decline in neuronal activity. It causes cognitive dysfunction characterized by apoptosis and DNA damage. A considerable aging hallmark is cellular senescence that involves epigenetic, genetic and environmental factors. The proliferative cessation of the cell cycle is irreversible and is a well-regulated process that has favourable as well as deleterious effects in the body. Cellular senescence helps in removal of damaged proteins from the cells and decreases autophagic flux. There is substantial telomere shortening, mitochondrial dysfunction and inflammation. Senescent cells upregulate SCAP (senescent cell anti-apoptotic pathway) and display distinct SASP (senescence-associated secretory phenotype) that hinder their death regardless of damage to cell organelles and DNA. Aging hallmarks, specifically senescence, are crucial for neurological disorders including Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, epilepsy and amyotrophic lateral sclerosis. Therefore, targeting senescence therapeutically may offer improved and extended lifespan. The therapeutic targets include SASP and SCAP that led to the advancement in senotherapeutic agents that cause senescent cell death selectively. The drugs that target the arrest of specific senescent cells are recognised as senolytics, while the drugs that target SASP are known as senomorphics. Here we discuss the mechanism of cellular senescence in several neurological disorders in addition to the advancements in senotherapeutics that help to ameliorate neurological insufficiency.