Research Projects

Mild Cognitive Impairment (MCI) is a cognitive decline that exceeds an individual's expected age and education level but does not significantly impact daily life. Over half of MCI cases progress to dementia within five years, making it a risk state for dementia. Neurodegenerative diseases like Alzheimer's disease (AD) are often associated with MCI, accounting for 60-80% of cases in individuals above 60 years of age. People with MCI due to AD show changes in biomarkers such as abnormal levels of beta-amyloid and hyper-phosphorylation of tau proteins. Metabolic disorders like Type 1 and Type II diabetes are also associated with cognitive impairment. Currently, available cholinesterase inhibitors therapies for cognitive impairment are limited and provide only symptomatic relief. There is a need to look for new mechanisms and pharmacological interventions for the treatment of MCI. The Transient Receptor Potential Channel (TRPC5) family has been implicated in oxidative stress and Ca2-mediated neuronal death, and TRPC5 channels have been implicated as a potential target for CNS diseases like anxiety, depression, Huntington's disease, epilepsy, and cerebral ischemia. This study aims to investigate the time-dependent expression of TRPC5 channels and the effects of pharmacological interventions targeting TRPC5 in cognitive impairment induced by A? and diabetes. The study will use TRPC5 modulators HC-070, Clemizole, and BTD to understand the role of TRPC5 and its crosstalk with mitochondrial dysfunctions in cognitive impairment pathology. Protein expression studies will be conducted to study molecular changes associated with TRPC5 modulation. Inhibition or downregulation of TRPC5 channels using pharmacological interventions/siRNA might reverse these pathological events and provide neuroprotection from cognitive impairment.