Research Projects

Alzheimer's disease (AD) is the leading cause of dementia, characterized by progressive memory and cognition loss. Down's Syndrome (DS) is at high risk of developing pathology similar to AD, with 50-70% of DS patients acquiring dementia by 60-70 years of age. Inflammation plays a key role in AD pathogenesis, and an absolute diagnosis can only occur after pathological analysis is performed on brain tissue. High concentrations of calcium in the cytosol promote beta amyloid protein production and mediate tau protein phosphorylation. Mitochondria calcium uniporter (MCU) is one of the most selective calcium transporting complexes in the mitochondria, playing a pivotal role in calcium signaling critical for the central nervous system's functioning. The precise physiological function of amyloid precursor protein (APP) remains unclear, but overexpression shows a positive effect on cell health and growth. The proposed study aims to understand the link between mitochondrial dysfunction, calcium homeostasis, and production of ROS in DS associated with AD. An imbalance in calcium homeostasis results in a cascade of events explaining many of AD pathophysiology. MCU has also displayed neuroprotective properties, which could pave a path for potential treatment of neurodegenerative diseases. Research in this area is needed for better understanding of the role of MCU in neurodegeneration and the application of the MCU antagonist in neurodegenerative disorder therapy. Mitochondrial-targeting drugs for mitochondrial diseases are an exciting, novel area of research with great therapeutic potential. The outcome of this study will open a novel view of treatment on DS associated with AD, providing unique opportunities to develop novel therapeutic targeting for the MCU complex or its subunits.