Use of autophagy inducers as microtubule stabilizing drugs to promote nerve regeneration

A technology of inducers and microtubules, which can be used in microorganisms, drug combinations, nervous system diseases, etc., and can solve the problems of lack of conclusion in the central nervous system.

Active Publication Date: 2022-01-21
CENT FOR EXCELLENCE IN BRAIN SCI & INTELLIGENCE TECH CHINESE ACAD OF SCI
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Problems solved by technology

However, at present, whether the regulation of autophagy level can promote the axon regeneration of adult mammalian central nervous system is still inconclusive.

Method used

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  • Use of autophagy inducers as microtubule stabilizing drugs to promote nerve regeneration
  • Use of autophagy inducers as microtubule stabilizing drugs to promote nerve regeneration
  • Use of autophagy inducers as microtubule stabilizing drugs to promote nerve regeneration

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Embodiment Construction

[0024] Inducing autophagy to study the role of autophagy in axon regeneration after axon injury is a straightforward approach, but most compounds that induce autophagy have uncontrollable side effects. In the present invention, we mainly use a polypeptide Tat-beclin1 that can specifically enhance autophagy in vivo and in vitro to induce autophagy. We found in rat cortical neurons cultured in vitro that increased autophagy can stabilize microtubules by degrading a neuron-specific microtubule destabilizing protein (SCG10) and promote the growth of neuronal neurites. In addition, in a mouse model of spinal cord injury, local administration of Tat-beclin1 treatment can significantly reduce the retraction of axons after spinal cord injury, promote axon regeneration and recovery of motor function in mice. The present invention discovers that autophagy can stabilize the key function of neuron microtubules, and proposes an autophagy inducer represented by Tat-beclin1 as a potential th...

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Abstract

The present invention provides the use of an autophagy inducer as a microtubule stabilizing drug to promote nerve regeneration. Specifically, the present invention provides for promoting neurite outgrowth of cultured central neurons in vitro and attenuating the inhibitory effect of myelin on neurite outgrowth, or stabilizing the microtubules of CNS damaged neurons, or reducing the withdrawal of CNS axons after injury A method of either reversing vesicle formation, or promoting axonal regeneration following central nerve injury, the method comprising the step of contacting the isolated neuron with an autophagy-inducing agent to induce autophagy. The present invention also provides the use of the autophagy inducer in the preparation of medicine. The method of the present invention can significantly reduce the retraction of axons after spinal cord injury, and promote axon regeneration and motor function recovery.

Description

technical field [0001] The invention relates to the use of an autophagy inducer as a microtubule stabilizing drug to promote nerve regeneration. Background technique [0002] The central nervous system is composed of the brain and spinal cord and is the most important part of the human nervous system. The spinal cord is the pathway of connections between the peripheral nerves and the brain. Spinal cord injury refers to damage to the spinal cord due to trauma (e.g. fall, car accident), disease or degeneration (e.g. cancer, inflammation), etc. According to World Health Organization estimates, the annual global incidence rate is 40 to 80 cases per million people, and it shows a trend of increasing year by year. The axon trunk in the spinal cord is difficult to regenerate after being damaged, which leads to serious dysfunction of the limbs below the damaged segment, a series of complications and high mortality, which brings serious physical and mental harm to the patient himse...

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C12N5/0793C12Q1/02A61K38/16A61K45/06A61P25/28
CPCA61K38/16A61K45/06G01N33/502G01N33/5058C12N5/0619C12N2501/065C12N2501/998C12N2501/999C12N2501/727C12N2501/734A61K2300/00
Inventor 罗振革何苗
Owner CENT FOR EXCELLENCE IN BRAIN SCI & INTELLIGENCE TECH CHINESE ACAD OF SCI
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