Summary: A new study shows a novel protein, lipin1, that regulates neurons rejuvenation in the central nervous system, offering fresh promise for treating spinal cord injuries. The study shows that inhibiting lipin1 increases lipid metabolism in cells, activating important processes like mTOR and STAT3 that promote muscle renewal.
This approach drastically improved spinal cord axon regeneration, suggesting a possible novel therapy for CNS injuries. The results open the door for more studies on using this gene-based approach to treat spinal cord injuries.
Important Information:
- Lipin1 regulates fat digestion to promote CNS axon renewal.
- Inhibiting lipin1 activates the mTOR and STAT3 channels, important for nerve repair.
- This finding opens up new avenues of care for spinal cord injuries.
Origin: HKUST
A collaborative study in neuroscience, spearheaded by a research team of the Hong Kong University of Science and Technology ( HKUST ), sheds light on new possibilities for treating central nervous system ( CNS ) injuries, as published in , PNAS.
Scientists have made a major step forward in recovering broken neural networks by the discovery of a book gene that regulates the renewal of various types of CNS axons.
Adult vertebrate CNS’s inability to fix itself poses a significant challenge when treating conditions like spinal cord damage, which frequently leads to permanent disabilities like paralysis.
A preliminary research conducted by Prof. Kai LIU’s team from the Division of Living Science at HKUST, which revealed that lipin1 is essential for controlling neurons renewal by influencing fat digestion in cells, was published in Neuron in 2019.
However, more research is required to fully realize the intricate neurons rejuvenation mechanisms and how they can be used for treatments for spinal cord injuries.
When inhibited in retinal ganglion cells, lipin1 is an enzyme that promotes nerve repair by shifting lipid synthesis from storage lipids to phospholipids while also producing signaling lipids like phosphatidic acid ( PA ) and lysophosphatidic acid ( LPA ). These fat activate vital cellular pathways, including the mTOR route, which is important for cell growth and success.
In this new study, the research team led by Prof. Kai Liu designed a tale shRNA targeting lipin1 rna and encapsulated it in an AAV vectors for distribution to cells, which can reduce lipin1 levels by 63 %.
They discovered that lowering lipin1 levels in neurons raised the levels of PA and LPA, leading to an increase in mTOR detection and STAT3 detection.
These alterations substantially boosted muscle regeneration. This finding points to a crucial responsibility that lipin1-PA/LPA-mTOR plays in preventing muscle regeneration following injury.
With few options for treatment, spinal cord injuries are a damaging situation. Pten’s role as a tumor suppressor makes it more difficult to use in clinical trials, which has led to the development of novel therapeutic approaches despite the fact that it has been recognized by researchers in recent years as a strong target for promoting neuron regeneration. A bundle of nerve fibers that control fine motor skills connect the brain to the spinal cord, known as the corticospinal tract ( CST ).
Using a rigorous complete spinal cord injury model, the researchers demonstrated that lipin1 knockdown ( KD ) promotes robust CST axon regeneration. Amazingly, the regenerative influence of lipin1 KD is similar, if not superior, to that of Pten termination.
The researchers examined the renewal of ascending visual axons and discovered that lipin1 KD also significantly increased the rejuvenation of these visual axons in order to see if it could even promote regeneration in another spinal tracts.
Additionally, this recent study demonstrates that blocking lipin1 results in the activation of mTOR and STAT3 signaling processes through PA and LPA, which ultimately affects CNS neurons ‘ ability to heal.
His study identifies lipin1 as a maintained goal that regulates neuron regeneration in a variety of settings, opening up a promising new path to treating spinal cord injuries.
This study was a collaborative work between team led by Prof. Kai Liu at HKUST, Prof. Zhongping YAO at The Hong Kong Polytechnic University, HKUST President Prof. Nancy Internet and Division of Life Science Prof. Amy FU, and Prof. Jacque Internet at The Chinese University of Hong Kong.
Funding: The study was supported by grants from the Hong Kong Areas of Excellence ( AoE ) Scheme by Research Grant Council, Innovation and Technology Commission, Health and Medical Research Fund, National Natural Science Foundation of China, Guangzhou Key Projects of Brain Science and Brain-Like Intelligence Technology, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Nan Fung Life Sciences, and Guangdong Natural Science Foundation.
About this information from neuroscience and genetics research
Author: Victor Lee
Source: HKUST
Contact: Victor Lee – HKUST
Image: The image is credited to Neuroscience News
Original Research: Start exposure.
” Lipin1 loss location cerebral signaling pathways to encourage motor and sensory neurons renewal after spinal cord injury” by Kai LIU et cetera. Journal
Abstract
After a spinal cord injury, lipin1 loss coordinates synaptic signaling pathways to encourage motor and sensory axon regeneration.
Adult central nervous system ( CNS ) neurons down-regulate growth programs after injury, leading to persistent regeneration failure. During neurons regeneration, membrane components need to be synthesized through planned lipid metabolism.
But, molecules also function as mobile signaling substances. Is fat signaling involved in neuron regeneration still a mystery.
In this study, we showed that lipin1 orchestrates mechanistic target of rapamycin (mTOR ) and STAT3 signaling pathways to determine axon regeneration. We created a mTOR-lipin1-phosphatidic acid/lysophosphatidic acid-mTOR loop that serves as a good feedback antagonistic signaling, which is responsible for the consistent suppression of CNS axon rejuvenation following injury.
Additionally, lipin1 knockdown ( KD ) promotes CST regeneration following complete spinal cord injury (SCI) and increases corticospinal tract ( CST ) sprouting following unilateral pyramidotomy. However, lipin1 KD enhances visual axon rejuvenation after SCI.
Nevertheless, our study demonstrates that lipin1 serves as a central regulator of the CNS cells ‘ mTOR and STAT3 signaling pathways and suggests that lipin1 might be a promising therapeutic goal for promoting the renewal of motor and sensory neurons following SCI.
