A multi enzyme study reviewing the role of target enzymes in Alzheimer’s disease and unveiling potential inhibitors with insights on their present and future assessment

Abstract

One of the most common types of Dementia mostly affecting people over the age of 65 is Alzheimer’s Disease. Characterized by various Neuropsychiatric Symptoms such as, memory loss, cognitive impairment, mood and behavioral disturbances leading to a poor life style. WHO 2021 Global status report states that the cases of dementia will drastically increase from 55 million in 2019 to 139 million in 2050 and the total amount paid for health care, long-term care and hospice services by dementia patients is $360 billion (estimated) in 2024. This is alarming and requires serious attention. To do so, first and foremost, identification of the targets involved in the pathogenesis of the disease is necessary. In Alzheimer’s disease, there are two highly accepted hypothesis, Tau and Amyloid beta (Aβ). Extensive research on these Hypothesis has revealed some potential target enzymes such as, Beta-site amyloid precursor protein cleaving enzyme 1 (BACE-1), Monoamine oxidases (MAO), GSK-3 (Glycogen synthase kinase-3) and Cholinesterases. Scientists tried to leverage, enzyme inhibition as a way to modulate the activity of these enzymes and modulation of enzymes was perceived to be affecting the progression and symptoms of the disease significantly. From there, enzyme inhibition has been thought to therapeutically affect the pathogenesis of disease. Some drugs which have undergone clinical trials but were not able to complete them due to side effects and lack of efficacy are Crenezumab (targeting Aβ), LMTM (TRx0237) (targeting Tau) and verubecestat (BACE-1 inhibitor) were terminated in clinical trials. In this review we have inquired the role of BACE-1, MAO, GSK-3 and Cholinesterases in Alzheimer’s Disease and unveiled Potential Inhibitors, which may fulfill the demand of a novel drug.

Target Enzymes involved in the pathogenesis of Alzheimer’s Disease and Therapeutic approach.