In this intriguing episode, we are privileged to host Dr. Chatterjee, a renowned expert studying the mechanisms of memory loss in Alzheimer's disease and related dementias (ADRD). Despite extensive research, the underlying causes of memory loss associated with ADRD remain unclear, and effective treatments are currently non-existent.

Dr. Chatterjee's groundbreaking work focuses on the nuclear receptor 4a (Nr4a) family of transcriptional regulatory proteins. His team has uncovered that these Nr4a proteins play a crucial role in controlling the transcription of genes that encode endoplasmic reticulum (ER) chaperones. These chaperones are responsible for folding and transporting plasticity-related proteins to the cell surface, which is a critical process in long-lasting forms of synaptic plasticity and memory.

Significantly, his research has linked the dysregulation of Nr4a transcription factors and ER chaperones to ADRD. In a promising development, the team found that overexpression of Nr4a1 or the chaperone Hspa5 can help mitigate long-term memory deficits in a tau-based mouse model of ADRD.

These exciting findings not only establish a unique molecular concept underlying long-term memory but also offer invaluable insights into the mechanistic basis of cognitive deficits in dementia, opening up potential avenues for innovative therapeutic approaches.

Join us as we delve into the details of this fascinating research with Dr. Chatterjee.

Keywords: Alzheimer's disease, dementia, memory loss, Nr4a proteins, transcription factors, ER chaperones, synaptic plasticity, Hspa5, long-term memory, Dr. Chatterjee.

https://doi.org/10.1126/sciadv.abm6063 Endoplasmic reticulum chaperone genes encode effectors of long-term memory.