Ashcharya Rishi / Chemistry & Biochemistry / Faculty Mentor: Subhrangsu Mandal
Alzheimer’s disease (AD) is a neurodegenerative disorder affecting nearly 7 million Americans and 50 million people worldwide. Characterized by amyloid-beta (Aβ) plaques, tau hyperphosphorylation, and cognitive decline, AD is increasingly linked to neuroinflammation mediated by microglia, the brain’s resident immune cells. A key factor in maintaining synaptic plasticity and cognitive health, brain-derived neurotrophic factor (BDNF) has been found to decrease in neurodegenerative diseases like AD, impacting neuron survival and function. Recent studies, including our own, suggest that BDNF expression is regulated by the long non-coding RNA (LncRNA) HOTAIR, emphasizing a role for LncRNAs in brain health and disease. Our research aims to identify novel LncRNAs associated with Aꞵ-induced neuroinflammation and microglial activation in AD. We have observed that Aꞵ-induced neuroinflammation downregulates BDNF in microglia, suggesting that LncRNAs may play key regulatory players in neuroinflammatory pathways. In parallel, our studies in human THP1-derived macrophages (THP1-M) have revealed novel LncRNAs involved in inflammatory responses, some potentially also involved in A induced neuroinflammation. This work will focus on elucidating the mechanisms by which these novel LncRNAs modulate Aꞵ-induced neuroinflammation and contribute to AD progression. Furthermore, this research could uncover potential diagnostic and therapeutic targets for Alzheimer’s disease.
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