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Last update 08 May 2025

NRL

Last update 08 May 2025

Basic Info

Synonyms

D14S46E, neural retina leucine zipper, Neural retina-specific leucine zipper protein

+ [3]

Introduction

Acts as a transcriptional activator which regulates the expression of several rod-specific genes, including RHO and PDE6B (PubMed:21981118). Functions also as a transcriptional coactivator, stimulating transcription mediated by the transcription factor CRX and NR2E3 (PubMed:17335001). Binds in a sequence-specific manner to the rhodopsin promoter (PubMed:17335001).

Drugs associated with NRL

WO2023049716

Patent Mining

Target

NRL

Mechanism-

Active Org.

Novartis AG

Originator Org.

Novartis AG

Active Indication

Other Diseases [+1]

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with NRL

100 Translational Medicine associated with NRL

0 Patents (Medical) associated with NRL

480

Literatures (Medical) associated with NRL

01 Apr 2025·Experimental Eye Research

Daily proteome variations highlight sustained metabolic activity in cone cells of Nrl knockout mice

Article

Author: Wongchitrat, Prapimpun ; Lapmanee, Sarawut ; Yasawong, Montri ; Pannengpetch, Supitcha ; Nakorn, Piyada Na ; Sandu, Cristina ; Felder-Schmittbuhl, Marie-Paule ; Khaenam, Prasong

Vision is a highly rhythmic function adapted to daily changes in light intensity. Rhythms disruption is known to compromise retinal health and visual function. This study investigates expression patterns of cone proteins over the 24-h daily cycle in order to understand the molecular bases of cone cyclic physiology. Cones were isolated by vibratome-sectioning from Nrl knockout mice at four time points across the 24-h LD (Light-Dark) cycle and protein extracts were quantified by label-free LC-MS/MS. The resulting protein data was then submitted to MetaCycle analysis to identify proteins with rhythmic expression patterns and associated functions. Cyclic profiles were further validated by SWATH-MS analysis. A total of 1208 proteins were identified. Rhythmic expression patterns were found for 319 proteins, categorized into four clusters based on intensity variation. SWATH-MS analysis validated the approach. Functional enrichment analysis revealed proteins critical for photoreceptor function, including those involved in phototransduction, oxidative phosphorylation, RNA processing, proteostasis, transport, synaptic function and cilia biogenesis. These findings provide a unique dataset of rhythmic cone proteins, potentially crucial for elucidating cone cell physiology and visual function. This knowledge can empower future research on preventing and treating vision impairment.

17 Feb 2025·Human Molecular Genetics

Integration of multiomic data identifies core-module of inherited-retinal diseases

Article

Author: Singh, Ajeet ; Ratnapriya, Rinki

AbstractHuman diseases with similar phenotypes can be interconnected through shared biological pathways, genes, or molecular mechanisms. Inherited retinal diseases (IRDs) cause photoreceptor dysfunction due to mutations in approximately 300 genes, affecting visual transduction, photoreceptor morphogenesis, and transcription factors, suggesting common pathobiological mechanisms. This study examined the functional relationship between known IRDs genes by integrating binding sites and gene expression data from the key photoreceptor transcription factors (TFs), Crx and Nrl. We show that the targets of these TFs were enriched in IRDs causal genes. Co-expression network analysis revealed that IRD-centric networks were disrupted when Crx and Nrl were knocked out. Finally, we identified a highly connected core module comprising 14 IRD and 39 target genes, of which 29 were dysregulated in the rod photoreceptors of the four IRD mouse models. These findings offer a network-based interpretation of IRDs, aiding in the identification of common mechanisms, prioritizing genes for novel disease gene identification, and informing the development of gene-agnostic therapies for IRDs.

01 Jan 2025·Advances in Experimental Medicine and Biology

Stimulation of Thyroid Hormone Signaling Induces Stress Responses in Mouse Retina

Article

Author: Li, Shujuan ; Ma, Hongwei ; Ding, Xi-Qin ; Yang, Fan

Thyroid hormone (TH) signaling is essential for cell proliferation, differentiation, and metabolic homeostasis. In the retina, TH signaling regulates retinal development, cone opsin expression, and photoreceptor viability. Suppressing TH signaling protects photoreceptors in mouse models of retinal degeneration whereas excessive TH signaling induces photoreceptor degeneration in mice. This work examined stress responses in the mouse retina after stimulation of TH signaling. C57BL/6 and Nrl^-/- mice received triiodothyronine (T3, 0.5 and 1.5 μg/mouse/day, s.c.) for 15 or 5 days, respectively, starting on postnatal day 10, and were then analyzed for retinal stress responses/oxidative damage and mitochondrial function. Treatment with T3 induced oxidative damage and activation of Müller cells and microglia in the retina. Moreover, treatment with T3 reduced mitochondrial respiration activity and ATP production in the retina. This work demonstrates the detrimental effect of excessive TH signaling on retinal homeostasis and provides insight into the mechanisms underlying excessive TH signaling-induced retinal degeneration.

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