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Application of inhibitor of acyl-CoA synthetase long chain family member 4 to treatment of Parkinson's disease

A long-chain fatty acyl-coenzyme and synthetase technology, which is used in the treatment of Parkinson's disease, the field of inhibitors of long-chain fatty acyl-CoA synthase 4, and can solve the problem of inability to take care of themselves, decreased quality of life, dysphagia, etc. question

Pending Publication Date: 2021-04-02
WEST CHINA HOSPITAL SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Patients in the late stage of the disease are often unable to take care of themselves due to balance disorders, falls, freezing of gait, dysphagia and language barriers, and even lie in bed for a long time, seriously reducing the quality of life

Method used

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  • Application of inhibitor of acyl-CoA synthetase long chain family member 4 to treatment of Parkinson's disease
  • Application of inhibitor of acyl-CoA synthetase long chain family member 4 to treatment of Parkinson's disease
  • Application of inhibitor of acyl-CoA synthetase long chain family member 4 to treatment of Parkinson's disease

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Experimental program
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Effect test

Embodiment 1

[0059] Based on the published human database GSE20141 data, the transcriptome data of long-chain acyl-CoA synthetase 4 was statistically analyzed, and the long-chain acyl-CoA synthetase 4 gene (ENSG00000068366) was found in SNpc of patients with Parkinson's disease Increased expression ( figure 1 In a), gene expression also increased in serum ( figure 1 Middle b, c).

Embodiment 2

[0061] 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can be dehydrogenated to MPP in substantia nigra cells + Ions, which inhibit the mitochondrial complex enzymes and cause the cell to die. MPTP is one of the commonly used drugs to make animal models of Parkinson's disease.

[0062] C57 mice were intraperitoneally injected with MPTP (20 mg / kg), four times in eight hours, once every two hours. Behavioral tests were carried out from day 19 to day 21 after injection. The pole-climbing test showed that MPTP-injected mice turned their heads significantly longer, and the open-field test showed that the movement speed of MPTP-injected mice was significantly slower, indicating that the mice's motor ability was impaired ( figure 2 Middle b, c): On the 21st day, the mice were euthanized, and after perfusion with PBS, the expression of Tyrosine hydroxylase (Tyrosinehydroxylase) and ACSL4 was detected in the substantia nigra of the left brain, and the right brain was soaked in 4...

Embodiment 3

[0064] The in vivo application of AAV virus vectors in the nervous system has the advantages of safety, high efficiency and low toxicity, and is very suitable for the research of the nervous system. Knockdown of ACSL4 expression in the substantia nigra was achieved by injecting the AAV8-ACSL4 virus vector capable of knocking out the mouse ACSL4 gene in the substantia nigra of mice ( image 3 Middle e), 30 days after virus injection, the MPTP model of Parkinson's disease was constructed, and the protective effect of substantia nigra ACSL4 knockout on the Parkinson's disease model was evaluated by behavioral detection and pathological section detection. The results showed that AAV8-mediated ACSL4 gene knockout could alleviate the motor impairment in Parkinson's disease model mice ( image 3 Middle a-d) and the reduction of expression of tyrosine hydroxylase after rescue MPTP modeling ( Figure 4 Middle a, b) and reduce the death of dopamine neurons ( Figure 4 Middle c, d).

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Abstract

The invention discloses application of inhibitor of acyl-CoA synthetase long chain family member 4 to treatment of the Parkinson's disease, and relates to the technical field of Parkinson's disease treatment. The invention discloses the application of the inhibitor of the acyl-CoA synthetase long chain family member 4 to preparation of a drug for preventing or treating the Parkinson's disease. Byresearch, the invention finds that, by taking the acyl-CoA synthetase long chain family member 4 (ACSL4) as the target, related symptoms of the Parkinson's disease can be improved by using the inhibitor of the ACSL4, and the inhibitor of the ACSL4 has a treatment effect on the Parkinson's disease; and the invention provides a new target and strategy for the treatment of the Parkinson's disease.

Description

technical field [0001] The invention relates to the technical field of Parkinson's disease treatment, in particular to the application of an inhibitor of long-chain fatty acyl-CoA synthetase 4 in the treatment of Parkinson's disease. Background technique [0002] Parkinson's disease (PD) is a neurodegenerative disease that occurs mainly in the elderly, mainly caused by the loss of brain cells that can produce dopamine. The main clinical feature is dyskinesia, including progressive bradykinesia, muscle rigidity, resting tremor, and abnormal posture and gait. In addition, it can also be accompanied by a large number of non-motor symptoms (NMS), such as hyposmia, constipation, depression, and sleep disturbance. With the progress of the disease, motor symptoms and non-motor symptoms gradually aggravate, and motor complications often appear in the later stage of the disease, including the decline of drug efficacy, "on-off" phenomenon, dyskinesia, etc. Patients in the late stage ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K31/4439A61P25/16
CPCA61K45/00A61K31/4439A61P25/16
Inventor 雷鹏熊欢唐飞
Owner WEST CHINA HOSPITAL SICHUAN UNIV
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