Abstract:
파킨슨병은 뇌의 흑색질 내에서 도파민 뉴런이 점차 상실되는 신경퇴행성 질환이다. 리보솜 단백질 S3 (rpS3)는 단백질 합성, 항산화 및 UV 엔도뉴클리에이즈 Ⅲ 활성과 같은 다양한 기능을 수행한다. 본 발명자들은 앞선 연구에서 PEP-1-rpS3 융합단백질이 피부염증을 억제하고 뇌허혈 손상에서 신경보호효과를 나타냄을 밝혔다. 본 발명자들은 PEP-1-rpS3 융합단백질이 SH-SY5Y 신경아세포종 세포 및 파킨슨병 동물모델에서 산화 스트레스로부터 도파민 뉴런을 보호할 수 있음을 밝혀내었다. PEP-1-rpS3 융합단백질은 SH-SY5Y 세포 내로 그리고 뇌의 흑색질 내로 잘 이동함을 웨스턴 블랏 분석으로 확인하였다. PEP-1-rpS3 융합단백질은 MPP + 로 유도되는 활성산소종 생성 및 DNA 조각화를 현저히 저해하였으며, 결과적으로 SH-SY5Y 세포의 생존을 유도했다. 신경보호 효과는 PEP-1-rpS3 융합단백질이 친-자기세로사멸 매개자 및 항-자기세포사멸 매개자의 수준에 영향을 미침으로써 얻어진다. 나아가, TH 항체 및 크레실 바이올렛 염색을 이용한 면역조직화학 분석 데이타는 PEP-1-rpS3 융합단백질이 MPTP와 같은 산화 스트레스에 대하여 흑색질 내의 도파민 세포를 현저히 보호함을 나타낸다. 따라서, PEP-1-rpS3 융합단백질은 파킨슨병의 예방 및 치료 용도로 이용 가능하다.
Abstract:
PURPOSE: A pharmaceutical composition containing PEP1-1-rpS3 fusion proteins for preventing and treating Parkinson's disease is provided to remarkably protect dopaminergic cells of substantia nigra from oxidative stresses such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). CONSTITUTION: A pharmaceutical composition for preventing and treating Parkinson's disease contains rpS fusion proteins which are prepared by covalent bond of a protein transport domain at N-terminal and/or C-terminal of rpS protein. The protein transport domain is selected among: a protein transport domain comprising a hydrophobic domain which consists of 15-30 amino acids containing 5 or more tryptophan, hydrophilic domains with four or more lysine, and a spacer which separates two domains; an oligolysine protein transport domain which consists of 6-12 lysine; an oligoarginine protein transport domain which consists of 56-12 arginine; and oligo (lysine, arginine) protein transport domain which consists of 6-12 lysine or arginine.
Abstract:
The present invention relates to a pharmaceutical composition for preventing or treating inflammatory arthritis, and more specifically, to a pharmaceutical composition for preventing or treating inflammatory arthritis containing fusion protein of FK506 binding protein which can go through the inside of cartilaginous tissue as an active ingredient.
Abstract:
Phosphoprotein enriched in astrocytes-15 (PEA-15) is a small protein created in neurons or astrocytic cells in brain. This protein which is a multi-functional protein can increase the cell survival rate thanks to its antiapoptotic and proapoptotic properties. Parkinson's disease is a neurodegenerative disease that dopamine neurons are reduced in substantia nigra in brain. The inventers found out that PEP-1-PEA-15 fusion protein can protect dopamine neurons from oxidation stress in SH-SY5Y neuroblastom cells and animals suffering from Parkinson's disease. It is confirmed that PEP-1-PEA-15 fusion protein can be transferred to SH-SY5Y cells and substantia nigra through western blot analysis. PEP-1-PEA-15 fusion protein prevents the active oxygen species production DNA tessellation induced to MPP+ and induces SH-SY5Y cell survival. Transmitted PEP-1-PEA-15 fusion protein improves the expression level of Bcl-2 protein but reduces the impression level of Bax protein. Also, PEP-1-PEA-15 fusion protein is transmitted to substantia nigra and prevents dopamine neuron cell death in substantia nigra. Therefore, PEP-1-PEA-15 fusion protein can prevent and treat Parkinson's disease.
Abstract:
PURPOSE: A pharmaceutical composition containing cell permeable rpS3 fusion protein is provided to smoothly deliver rpS3 fusion proteins into neural cells and to prevent the neural cells from apoptosis. CONSTITUTION: A pharmaceutical composition for preventing and treating neural diseases contains a cell permeable rpS3 fusion protein having a protein transduction domain linked to at least one end among N-terminal and C-terminal of rpS3 protein by covalent bond. The protein transduction domain comprises: a non-hydrophilic domain containing 15-30 amino acids and 5 or more tryptophans; a hydrophilic domain containing 4 or more lysines; and a spacer which separates two domains the rpS3 fusion protein has an amino acid sequence of sequence number 7, 9, or 11.