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Endothelin B receptor inhibition rescues aging-dependent neuronal regenerative decline [scRNA-seq]

ABSTRACT: Endothelin B receptor inhibition rescues aging-dependent neuronal regenerative decline [scRNA-seq]

PROVIDER: PRJNA1269306 | ENA |

REPOSITORIES: ENA

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Endothelin B receptor inhibition rescues aging-dependent neuronal regenerative decline [snRNA-seq]

Project description:Peripheral sensory neurons regenerate their axons after injury to regain function, but this ability declines with age. The mechanisms behind this decline are not fully understood. While excessive production of endothelin 1 (ET-1), a potent vasoconstrictor, is linked to many diseases that increase with age, the role of ET-1 and its receptors in axon regeneration is unknown. Using single cell RNA sequencing, we show that satellite glial cells (SGCs), which completely envelop the sensory neuron soma residing in the dorsal root ganglia (DRG), express the endothelin B receptor (ETBR), while ET-1 is expressed by endothelial cells. Inhibition of ETBR ex-vivo in DRG explant cultures improves axon growth in both adult and aged conditions. In vivo, treatment with the FDA-approved compound, Bosentan, improves axon regeneration and reverses the age-dependent decrease in axonal regenerative capacity. Single-nuclei RNA sequencing and electron microscopy analyses reveal a decreased abundance of SGCs in aged mice compared to adult mice. Additionally, the decreased expression of connexin 43 (Cx43) in SGCs in aged mice after nerve injury is partially rescued by Bosentan treatment. These results reveal that inhibiting ETBR function enhances axon regeneration and rescues the age-dependent decrease in axonal regenerative capacity, providing a potential avenue for future therapies.

2025-07-17 | GSE298413 | GEO

Endothelin B receptor inhibition rescues aging-dependent neuronal regenerative decline [scRNA-seq]

2025-07-17 | GSE298412 | GEO

Endothelin B receptor inhibition rescues aging-dependent neuronal regenerative decline [snRNA-seq]

Project description:Endothelin B receptor inhibition rescues aging-dependent neuronal regenerative decline [snRNA-seq]

| PRJNA1269311 | ENA

TARGETING NEURONAL FTL1 RESCUES COGNITIVE IMPAIRMENTS IN AGING

Project description:Understanding cellular and molecular drivers of age-related cognitive decline is necessary to identify targets to restore cognition at old age. Here we report that ferritin light chain 1 (FTL1) is a pro-aging neuronal factor that impairs cognition. Targeting neuronal FTL1 in the hippocampi of aged mice elicits synaptic and metabolic-related molecular changes and rescues cognitive impairments. Our data identify neuronal FTL1 as a key molecular mediator of cognitive rejuvenation.

2024-12-01 | GSE249504 | GEO

Targeting neuronal FTL1 rescues cognitive impairments in aging

2025-07-08 | GSE249105 | GEO

TARGETING NEURONAL FTL1 RESCUES COGNITIVE IMPAIRMENTS IN AGING

Project description:TARGETING NEURONAL FTL1 RESCUES COGNITIVE IMPAIRMENTS IN AGING

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Targeting neuronal FTL1 rescues cognitive impairments in aging

Project description:Targeting neuronal FTL1 rescues cognitive impairments in aging

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MicroRNA-19a-PTEN axis is involved in the developmental decline of axon regenerative capacity in retinal ganglion cells

Project description:Irreversible blindness from glaucoma and optic neuropathies is attributed to retinal ganglion cells (RGCs) losing the ability to regenerate axons. While several transcription factors and proteins have demonstrated enhancement of axon regeneration after optic nerve injury, mechanisms contributing to the age-related decline in axon regenerative capacity remains elusive. Here, we show that microRNAs are differentially expressed during RGC development, and identify microRNA-19a (miR-19a) as a heterochronic marker; developmental decline of miR-19a relieves suppression of PTEN, a key regulator of axon regeneration, and serves as a temporal indicator of decreasing axon regenerative capacity. Intravitreal injection of miR-19a promotes axon regeneration after optic nerve crush in adult mice, and increases axon extension in RGCs isolated from aged human donors. This uncovers a previously unrecognized involvement of the miR-19a-PTEN axis in RGC axon regeneration, and demonstrates therapeutic potential of microRNA-mediated restoration of axon regenerative capacity via intravitreal injection in patients with optic neuropathies.

2020-07-04 | GSE102458 | GEO

Aging Decline of LEPR+ HSCs

Project description:Aging Decline of LEPR+ HSCs

| PRJNA913011 | ENA

Phosphoproteomics of endothelin signalling

Project description:Time resolved phosphorylation changes were measured the melanoma cell lines A2058 and UACC257. An endothelin B receptor knockout of UACC257 was processed in parallel. Protein abundance was also compared at the latest time point of the study (90 min) using DIA-SWATH

2019-10-09 | PXD012316 | Pride

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