Use of pak4 and crtc1 for treatment or diagnosis of brain degenerative disease

Inactive Publication Date: 2019-01-17
CHUNGBUK NAT UNIV IND ACADEMIC COOPERATION FOUND
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  • Abstract
  • Description
  • Claims
  • Application Information

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Benefits of technology

[0027]The present invention relates to use of PAK4 and CRTC1, and more specifically, to pharmaceutical compositions for the prevention or treatment of a degenerative brain disease including PAK4 (p21-activated kinase 4) or a CRTC1 activator as an effective ingredient, diagnostic kits and methods for screening a therapeutic drug. In the present invention, it has been found that when PAK4 has increased protein level and has increased activity by phosphorylation, it is possible to suppress dopaminergic neuronal death in a dege

Problems solved by technology

However, the exact cause thereof has not yet been found, and basic researches are being actively conducted to identify the cause.
However, since these drugs are incapable of reviving dead neurons, there are limitations that they are not intended for

Method used

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  • Use of pak4 and crtc1 for treatment or diagnosis of brain degenerative disease
  • Use of pak4 and crtc1 for treatment or diagnosis of brain degenerative disease
  • Use of pak4 and crtc1 for treatment or diagnosis of brain degenerative disease

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Preparation Examples

[0088]Materials and Experimental Methods

[0089]The commercial sources of the materials used in the following experiments and the experimental methods are as described below. In addition, the samples from patients with Parkinson's disease used in the experiments were obtained from Victoria Brain Bank Network (VBBN), and the experimental methods were conducted under the conditions approved by the Ethics Review Committee of the Institutional Review Board of Chungbuk National University (approval number: CBNU-IRB-2011-T01).

[0090]Also, the rats used in the experiments were 260 to 280 g of Female Sprague-Dawley rats obtained from Taconi, and kept under 12-hour light / dark cycles while being fed a normal diet. Animal experiments were also conducted under the conditions approved by the Ethics Review Committee of Chungbuk National University for Animal Experiments (approval number: CBNUA-400-12-02).

[0091]In addition, the human tissues used in the experiments were obtained f...

Example

Example 1

[0140]Analysis for Neuroprotective Activity of PAK4 in Parkinson's Disease

[0141]Expression levels of pPAK4 and PAK4 in Parkinson's disease were analyzed. As for samples for analysis, the tissue samples obtained from the subjects for experiments in Table 1 above were immunoblotted with pPAK4 and PAK4 antibodies.

[0142]As a result, as shown in FIG. 1, it has been shown that expressions of pPAK4 and PAK4 were all reduced in the samples derived from patients with Parkinson's disease compared to the control samples. In addition, it has been shown that the expression level of TH, a marker of DA neurons, was also reduced in the Parkinson's disease group compared to the control group (see FIGS. 1A and 1B). Besides, the expression levels of pPAK4 and PAK4 in living TH-positive DA neurons were analyzed. As a result, it has been shown that the expression in DA neurons of the Parkinson's disease group was reduced compared to the control groups (age-matched control, young control) (see F...

Example

Example 2

[0143]Analysis of Expression Levels of PAK4 and Phosphorylated-PAK4 in Animal Model of Parkinson's Disease

[0144]After each brain tissue was obtained through the experimental procedure as described above in the rat animal model of Parkinson's disease induced by administration of 6-OHDA, the expression levels of PAK4 and phosphorylated-PAK4 were analyzed.

[0145]As a result, as shown in FIG. 2, it has been shown that the expression level of phosphorylated-PAK4 was significantly reduced in the samples from rats with Parkinson's disease induced by 6-OHDA, compared to the control without 6-OHDA administration (see FIGS. 2A to 2C).

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Abstract

The present invention relates to use of PAK4 and CRTC1 for the treatment or diagnosis of a degenerative brain disease. Specifically, the present invention relates to a pharmaceutical composition for the prevention or treatment of a degenerative brain disease comprising PAK4 (p21-activated kinase 4) or a PAK4 activator as an effective ingredient. In addition, the present invention relates to a pharmaceutical composition for the prevention or treatment of a degenerative brain disease comprising a CRTC1 expression enhancer or activator as an effective ingredient, a diagnostic kit for a degenerative brain disease comprising an agent for detecting CRTC1, and a method for screening a substance for the prevention or treatment of a degenerative brain disease, comprising (a) applying a candidate drug to brain tissue or brain cells containing CRTC1 gene or CRTC1 protein; (b) measuring the degree of phosphorylation in CRTC1; and (c) determining the candidate drug as a substance for the prevention or treatment of a degenerative brain disease when the measurement in step (b) indicates that the phosphorylation in CRTC1 is increased.

Description

BACKGROUND OF THE INVENTION(a) Field of the Invention[0001]The present invention relates to use of PAK4 and CRTC1 for the treatment or diagnosis of a degenerative brain disease.(b) Description of the Related Art[0002]A degenerative brain disease refers to a disease that occurs in the brain among other degenerative diseases occurring with age, and may be classified according to main symptoms and affected brain areas. It typically includes Alzheimer's disease or Parkinson's disease, or the like. A degenerative brain disease is known to be caused by neuronal death resulting from protein aggregation due to age-related neurodegeneration and other genetic / environmental factors. However, the exact cause thereof has not yet been found, and basic researches are being actively conducted to identify the cause.[0003]Along with Alzheimer's disease, Parkinson's disease is one of the typical degenerative neurological diseases occurring in old age. It affects about 1% of the population aged 65 year...

Claims

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Application Information

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IPC IPC(8): G01N33/50G01N33/68G01N33/53
CPCG01N33/5008G01N33/6812G01N2800/56G01N2800/52G01N2800/2835G01N33/53G01N33/5088G01N33/5058A61K38/16A61K39/395A61K48/005G01N33/5044G01N33/6896G01N2440/14
Inventor KIM, EUNG GOOKWON, SO YOONSHIN, EUN YOUNG
Owner CHUNGBUK NAT UNIV IND ACADEMIC COOPERATION FOUND
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