Journal article
Endoplasmic reticulum chaperone genes encode effectors of long-term memory
Science advances, Vol.8(12), pp.eabm6063-eabm6063
03/25/2022
DOI: 10.1126/sciadv.abm6063
PMCID: PMC8942353
PMID: 35319980
Abstract
The mechanisms underlying memory loss associated with Alzheimer's disease and related dementias (ADRD) remain unclear, and no effective treatments exist. Fundamental studies have shown that a set of transcriptional regulatory proteins of the nuclear receptor 4a (Nr4a) family serve as molecular switches for long-term memory. Here, we show that Nr4a proteins regulate the transcription of genes encoding chaperones that localize to the endoplasmic reticulum (ER). These chaperones fold and traffic plasticity-related proteins to the cell surface during long-lasting forms of synaptic plasticity and memory. Dysregulation of Nr4a transcription factors and ER chaperones is linked to ADRD, and overexpressing Nr4a1 or the chaperone Hspa5 ameliorates long-term memory deficits in a tau-based mouse model of ADRD, pointing toward innovative therapeutic approaches for treating memory loss. Our findings establish a unique molecular concept underlying long-term memory and provide insights into the mechanistic basis of cognitive deficits in dementia.
Details
- Title: Subtitle
- Endoplasmic reticulum chaperone genes encode effectors of long-term memory
- Creators
- Snehajyoti Chatterjee - University of IowaEthan Bahl - University of IowaUtsav Mukherjee - University of IowaEmily N Walsh - University of IowaMahesh Shivarama Shetty - University of IowaAmy L Yan - University of IowaYann Vanrobaeys - University of IowaJoseph D Lederman - University of IowaK Peter Giese - King's College LondonJacob Michaelson - University of IowaTed Abel - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Science advances, Vol.8(12), pp.eabm6063-eabm6063
- DOI
- 10.1126/sciadv.abm6063
- PMID
- 35319980
- PMCID
- PMC8942353
- NLM abbreviation
- Sci Adv
- eISSN
- 2375-2548
- Language
- English
- Date published
- 03/25/2022
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Communication Sciences and Disorders; Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
- Record Identifier
- 9984230139502771
Metrics
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