IN-SILICO STUDY TO REPURPOSE DJ1 BINDING COMPOUNDS FOR ALZHEIMER'S DISEASE AND PARKINSON'S RELATED DEMENTIA

Abstract

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common chronic neurodegenerative disorders affecting worldwide population and is expected to increase over the years. Alzheimer’s disease marked by agglomeration of beta amyloid and tau fibrillary tangles, exhibit loss of memory with time. While Parkinson’s disease is characterized by progressive loss of dopaminergic neurons of the substantia nigra that results into clinical symptoms like tremor, bradykinesia, rigidity, slower movement and postural instability. However, both AD and PD are associated with cognitive impairment leading to dementia along with other canonical symptoms. This proposes a cross link between the diseases and hence toxic proteins. Studies suggest the oxidized form of DJ-1, also an oncogene; has-been observed in patients with AD and PD. Recent work on finding compounds that can modulate the protein DJ1 has brought Compound-23 and Compound-B into focus as it has been observed to exert neuroprotective effect against neurodegeneration in PD model, proposing it to be a lead compound for PD therapies. Hence the overall objective of our work is to apply in-silico approaches to study the gene architecture of PARK7 along with the TFBEs to explore its role in PD pathology. Further, the study involves in-silico screening of common protein targets of AD and PDD, followed by performing comparative molecular docking of these compounds against the targets while using conventional drugs as control. This may pave the way for developing effective preventative and therapeutic strategies to treat this devastating disease.