We recently revealed that the axon endoplasmic reticulum resident transcription factor Luman/CREB3 (herein called Luman) serves as a unique retrograde injury signal in regulation of the intrinsic elongating form of sensory axon regeneration. Here, evidence supports that Luman contributes to axonal regeneration through regulation of the unfolded protein response (UPR) and cholesterol biosynthesis in adult rat sensory neurons. One day sciatic nerve crush injury triggered a robust increase in UPR-associated mRNA and protein expression in both neuronal cell bodies and the injured axons. Knockdown of Luman expression in 1 d injury-conditioned neurons by siRNA attenuated axonal outgrowth to 48% of control injured neurons and was concomitant with reduced UPR- and cholesterol biosynthesis-associated gene expression. UPR PCR-array analysis coupled with qRT-PCR identified and confirmed that four transcripts involved in cholesterol regulation were downregulated >2-fold by the Luman siRNA treatment of the injury-conditioned neurons. Further, the Luman siRNA-attenuated outgrowth could be significantly rescued by either cholesterol supplementation or 2 ng/ml of the UPR inducer tunicamycin, an amount determined to elevate the depressed UPR gene expression to a level equivalent of that observed with crush injury. Using these approaches, outgrowth increased significantly to 74% or 69% that of injury-conditioned controls, respectively. The identification of Luman as a regulator of the injury-induced UPR and cholesterol at levels that benefit the intrinsic ability of axotomized adult rat sensory neurons to undergo axonal regeneration reveals new therapeutic targets to bolster nerve repair.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6605466 | PMC |
http://dx.doi.org/10.1523/JNEUROSCI.0012-15.2015 | DOI Listing |
Invest Ophthalmol Vis Sci
January 2025
Department of Ophthalmology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Purpose: Inflammatory processes have been involved in diabetic retinopathy (DR). Interleukin (IL)-17A, a pro-inflammatory cytokine, is associated with DR occurrence and development. However, mechanisms underlying the IL-17A impact on DR need further investigations.
View Article and Find Full Text PDFInvest Ophthalmol Vis Sci
January 2025
Laboratory of Anatomy of Domestic Animals, National Key Laboratory of Veterinary Public Health and Safety, College of Veterinary Medicine, China Agricultural University, Haidian, Beijing, China.
Purpose: Because chickens have excellent light perception properties, this study focused on investigating whether monochromatic light can cause photodamage in chicken retinal ganglion cells (RGCs).
Methods: Post-hatching day chickens were exposed to four different light-emitting diode light environments for five weeks, respectively, monochromatic blue light (480 nm), green light (560 nm), red light (660 nm), or white light (6000 K). The mechanisms through which monochromatic light influences the structure of the chicken retina were analyzed by detecting the morphological structure of the retina, gene and protein expression levels, and the ultrastructure of the optic nerve.
Curr Opin Allergy Clin Immunol
February 2025
Specialist Allergy and Clinical Immunology, Rhinology Section, Royal National ENT and Eastman Dental Hospitals, University College London Hospitals NHS Foundation Trust, London, UK.
Purpose Of Review: To evaluate the role of neuroimmune signalling pathways in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP).
Recent Findings: The sinonasal mucosa is densely infiltrated by immune cells and neuronal structures that share an intimate spatial relationship within tissue compartments. Together, such neuroimmune units play a critical role in airway defence and homeostatic function.
Front Mol Neurosci
December 2024
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN, United States.
Introduction: The prostate is densely innervated like many visceral organs and glands. However, studies to date have focused on sympathetic and parasympathetic nerves and little attention has been given to the presence or function of sensory nerves in the prostate. Recent studies have highlighted a role for sensory nerves beyond perception of noxious stimuli, as anterograde release of neuropeptides from sensory nerves can affect vascular tone and local immune responses.
View Article and Find Full Text PDFInt J Biol Sci
January 2025
Department of Ophthalmology, The Second Hospital of Jilin University, Jilin University, Changchun 130000, Jilin, China.
Glaucoma is a neurodegenerative disorder marked by the loss of retinal ganglion cells (RGCs) and axonal degeneration, resulting in irreversible vision impairment. While intraocular pressure (IOP) is presently acknowledged as the sole modifiable risk factor, the sensitivity of RGCs to IOP varies among individuals. Consequently, progressive vision loss may ensue even when IOP is effectively managed.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!