Application of RABGGTB in diagnosis and treatment of amyotrophic lateral sclerosis

A technology for lateral sclerosis, muscular atrophy, applied in the field of biomedicine, which can solve the problem of lack of treatment methods

Active Publication Date: 2022-03-15
THE SECOND HOSPITAL OF HEBEI MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] ALS is still an incurable disease, and there is currently a lack of effective treatment methods. Riruta and Edaravone certified by the FDA in the United States have very limited therapeutic effects on it. Therefore, early diagnosis and early treatment are urgently needed to find effective therapeutic targets. Point to develop drugs to delay disease progression and prolong survival

Method used

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  • Application of RABGGTB in diagnosis and treatment of amyotrophic lateral sclerosis
  • Application of RABGGTB in diagnosis and treatment of amyotrophic lateral sclerosis
  • Application of RABGGTB in diagnosis and treatment of amyotrophic lateral sclerosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0082] Example 1. Overexpression of RABGGTB has a protective effect on SOD1G93A motor neurons

[0083] First, we verified the expression of endogenous RABGGTA and RABGGTB in NSC34-E and NSC34-hSOD1G93A cells, and the results showed that the expression of endogenous RABGGTA (α subunit of GGTase II) in NSC34-SOD1G93A cells was not significantly higher than that in NSC34-E Compared with NSC34-E, the expression of endogenous RABGGTB (β subunit of GGTase II) was significantly reduced ( figure 1 ).

[0084] Then, we overexpressed RABGGTB in ALS cell model: NSC34-hSOD1G93A cells by lentiviral transfection.

[0085] The results are shown in the figure: compared with NSC34-E, the viability of NSC34-hSOD1G93A cells decreased, and the CCK8 value of NSC34-hSOD1G93A cells increased after overexpression of RABGGTB, indicating that the cell viability was significantly increased ( figure 2 ).

[0086] Compared with NSC34-E, cleaved caspase-3 in NSC34-hSOD1G93A cells increased, and the ex...

Embodiment 2

[0088] Example 2. Overexpression of RABGGTB reduces SOD1 protein aggregation in NSC34-SOD1G93A cells

[0089] There is a large amount of SOD1 protein aggregation in the NSC34-hSOD1G93A cell model. Previous studies have confirmed that the abnormal aggregation of SOD1 protein in motor neurons is an important cause of neuron death, which is related to the occurrence of ALS. We detected the accumulation of SOD1 in each group of cells by immunofluorescence experiments.

[0090] The results showed that compared with NSC34-E, there was a large amount of accumulated SOD1 in NSC34-hSOD1G93A motor neurons, and the level of SOD1 in NSC34-hSOD1G93A motor neurons was significantly lower after overexpression of RABGGTB ( Figure 4 ), consistent with immunofluorescence results, Western blotting results showed that overexpression of RABGGTB reduced SOD1 aggregation in NSC34-hSOD1G93A cells ( Figure 5 ).

Embodiment 3

[0091] Example 3. Overexpression of RABGGTB improves autophagy in NSC34-hSOD1G93A cells

[0092] Studies have reported that NSC34-hSOD1G93A cells have abnormal autophagy, which leads to the inability to degrade the abnormally aggregated SOD1 protein. In order to clarify whether the overexpression of RABGGRTB affects autophagy, we detected the level of autophagy in each group of cells by immunofluorescence and Western blotting. The results showed that overexpression of RABGGTB could reduce the increased levels of LC3 and P62 in NSC34-hSOD1G93A cells ( Figure 6 , Figure 7 ), and improved the impairment of autophagic flux present in NSC34-hSOD1G93A cells.

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Abstract

The invention belongs to the field of biomedicine, and particularly relates to application of RABGGTB in diagnosis and treatment of amyotrophic lateral sclerosis. The invention also provides an application of RABGGTB in preparation of drugs for treating amyotrophic lateral sclerosis and protection of motor neurons. Specifically, the RABGGTB refers to a biological material for expressing the RABGGTB or promoting the expression of the RABGGTB, or a composition containing the biological material.

Description

technical field [0001] The invention belongs to the field of biomedicine, and in particular relates to the application of RABGGTB in the diagnosis and treatment of amyotrophic lateral sclerosis. Background technique [0002] Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of unknown cause, mainly involving motor neurons in the anterior horn of the spinal cord, brainstem and cerebral cortex, also known as motor neuron disease. The clinical manifestations are progressively aggravated muscle weakness, muscle atrophy, dysphagia, dysphagia, and positive pathological signs of tendon reflexes. Most of them die due to respiratory muscle paralysis and respiratory failure 3-5 years after the onset. Studies have shown that 4% of SALS and 20% of FALS patients have SOD1 (superoxide dismutase 1, Superoxide Dismutase 1) mutation. Mutant SOD1 proteins are prone to misfolding and form aggregates in motor neurons that require autophagy for degradation. Autopha...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61P25/00A61P21/00C12Q1/6883G01N33/573
CPCA61K45/00A61P25/00A61P21/00C12Q1/6883G01N33/573C12Q2600/158G01N2333/9116G01N2800/2878
Inventor 李睿刘亚玲齐伟静白琳马海阳高天初
Owner THE SECOND HOSPITAL OF HEBEI MEDICAL UNIV
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