Abstract

COMPARATIVE ANALYSIS OF SARACATINIB, NILOTINIB, AND DASATINIB BASED ON THEIR SAFETY, EFFICACY, AND TOLERABILITY IN TREATING ALZHEIMER’S DISEASE

Dhairya Arun Bheda*, Pranjali Dinesh Pawar, Avinash Rangaraju and Abhishek Rathod

Abstract

Alzheimer‟s disease (AD) is an age-related neurodegenerative disease with progressive cognitive impairment and it is estimated to affect 6.9 million Americans and about 152 million people worldwide by 2050. The main pathologic hallmarks of Alzheimer's Disease include the deposition of extracellular amyloid-beta plaques, intracellular neurofibrillary tangles of hyperphosphorylated tau protein, as well as neuroinflammation, which results in neuronal dystrophy and, therefore, comprehensive synaptic elimination. In recent years, Tyrosine Kinase Inhibitors such as saracatinib, dasatinib, and nilotinib have been attempted on human clinical trials for Alzheimer's Disease, to target each of these specific pathogenic events. For instance, saracatinib exhibits neuroprotective effects by stabilizing the functional Fyn kinase activity; thus, enhancing cognitive functions in animals. Similarly, nilotinib increases autophagy, which helps to deal with toxic protein aggregates, and dasatinib targets inflammation and removes senescent cells connected with neurodegeneration. Clinical trials have yielded mixed but encouraging outcomes. Saracatinib exhibited a favorable safety profile and potential cognitive benefits in mild to moderate Alzheimer‟s Disease patients. Dasatinib demonstrated central nervous system penetration and the ability to target neuroinflammatory processes. However, a persistent, compelling case-in-point and overall, long-term effectiveness and non-hazardous outcome have not been conclusively proven yet. Since most of the existing therapeutic modalities are palliative, these newly developed Tyrosine Kinase Inhibitors offer a different treatment strategy by targeting the molecular pathophysiology of the disease. Further investigation is necessary for the best promulgation of their pharmacological uses and improved treatment modes for this mechanically severe neurological illness.

Keywords: Neurodegeneration, Tau Tangles, Tyrosine kinase inhibitors, Safety, Efficacy, Tolerability.