» Articles » PMID: 38410073

Understanding the Unfolded Protein Response (UPR) Pathway: Insights into Neuropsychiatric Disorders and Therapeutic Potentials

Overview
Specialty Pharmacology
Date 2024 Feb 27
PMID 38410073
Authors
Affiliations
Soon will be listed here.
Abstract

The Unfolded Protein Response (UPR) serves as a critical cellular mechanism dedicated to maintaining protein homeostasis, primarily within the endoplasmic reticulum (ER). This pathway diligently responds to a variety of intracellular indicators of ER stress with the objective of reinstating balance by diminishing the accumulation of unfolded proteins, amplifying the ER's folding capacity, and eliminating slow-folding proteins. Prolonged ER stress and UPR irregularities have been linked to a range of neuropsychiatric disorders, including major depressive disorder, bipolar disorder, and schizophrenia. This review offers a comprehensive overview of the UPR pathway, delineating its activation mechanisms and its role in the pathophysiology of neuropsychiatric disorders. It highlights the intricate interplay within the UPR and its profound influence on brain function, synaptic perturbations, and neural developmental processes. Additionally, it explores evolving therapeutic strategies targeting the UPR within the context of these disorders, underscoring the necessity for precision and further research to effective treatments. The research findings presented in this work underscore the promising potential of UPR-focused therapeutic approaches to address the complex landscape of neuropsychiatric disorders, giving rise to optimism for improving outcomes for individuals facing these complex conditions.

Citing Articles

The Interplay Between Endoplasmic Reticulum Stress and Ferroptosis in Neurological Diseases.

Zhai T, Wang B, Shi C, Zhang C, Shen J, Feng X Neurochem Res. 2025; 50(2):99.

PMID: 39928173 DOI: 10.1007/s11064-025-04348-4.


Emerging and Promising Keywords in Biomolecules and Therapeutics for 21st Century Diseases.

Ko H, Lee C Biomol Ther (Seoul). 2024; 33(1):1-4.

PMID: 39725476 PMC: 11704395. DOI: 10.4062/biomolther.2024.007.


Dissecting Schizophrenia Biology Using Pleiotropy with Cognitive Genomics.

Bhattacharyya U, John J, Lencz T, Lam M medRxiv. 2024; .

PMID: 38699340 PMC: 11065000. DOI: 10.1101/2024.04.16.24305885.

References
1.
Nadarajah B, Parnavelas J . Modes of neuronal migration in the developing cerebral cortex. Nat Rev Neurosci. 2002; 3(6):423-32. DOI: 10.1038/nrn845. View

2.
Kawada K, Iekumo T, Saito R, Kaneko M, Mimori S, Nomura Y . Aberrant neuronal differentiation and inhibition of dendrite outgrowth resulting from endoplasmic reticulum stress. J Neurosci Res. 2014; 92(9):1122-33. PMC: 4320781. DOI: 10.1002/jnr.23389. View

3.
Reinhardt S, Schuck F, Grosgen S, Riemenschneider M, Hartmann T, Postina R . Unfolded protein response signaling by transcription factor XBP-1 regulates ADAM10 and is affected in Alzheimer's disease. FASEB J. 2013; 28(2):978-97. DOI: 10.1096/fj.13-234864. View

4.
Lee A . The glucose-regulated proteins: stress induction and clinical applications. Trends Biochem Sci. 2001; 26(8):504-10. DOI: 10.1016/s0968-0004(01)01908-9. View

5.
Wang M, Kaufman R . The impact of the endoplasmic reticulum protein-folding environment on cancer development. Nat Rev Cancer. 2014; 14(9):581-97. DOI: 10.1038/nrc3800. View