GDNF 蛋白, Rat (sf9, His)

Glial-cell-line-derived neurotrophic factor (GDNF), a neurotrophic factor belongs to the GDNF family ligands (GFLs)., promotes survival of dopamine neurons. GDNF demonstrates a variety of neuroprotective roles for mammalian neurons^[1]. GDNF Protein, Rat (sf9, His) is produced in Sf9 insect cells with a N-Terminal His-tag. It consists of 134 amino acids (S78-I211).

胶质细胞源性神经营养因子 (GDNF) 是一种 134 个氨基酸的蛋白质，属于 GDNF 家族配体 (GFL)。GDNF 蛋白广泛分布于中枢和周围神经系统。GDNF 的合成和分泌发生在许多细胞类型中，例如星形胶质细胞、少突胶质细胞和雪旺细胞等神经胶质细胞；运动神经元（MN）；和骨骼肌^[1]。
成熟的人类 GDNF 与小鼠、大鼠和犬科动物 GDNF 蛋白具有 91-92% 的氨基酸序列同一性。而小鼠 GDNF 与大鼠 GDNF 蛋白具有 99% 的氨基酸序列同一性。
GDNF 最初是从培养的 B49 大鼠神经胶质细胞中分离出来的，并被发现通过促进多巴胺摄取来增强原代培养物中多巴胺能神经元的存活和分化。与 TGF-β 超家族的其他成员类似，GDNF 首先作为前体蛋白（pro-GDNF）合成。经过一系列的蛋白质裂解和加工，211个氨基酸的pro-GDNF最终转化为活性且成熟的GDNF形式。GDNF 能够触发受体酪氨酸激酶 RET 磷酸化，其下游效应已被发现可促进神经元健康和存活。GDNF 与其受体的结合触发多个细胞内信号传导途径，这些信号传导途径在促进神经元-神经元和神经元-靶组织相互作用的发育、存活和维持中发挥作用。GDNF 的合成和调节已被证明在许多疾病、衰老、运动和成瘾中发生改变。GDNF 的神经保护作用可用于开发治疗方法，以改善神经退行性疾病，如肌萎缩侧索硬化症 (ALS)^[1]。
GDNF 是调节 MN 存活的有效神经营养因子在周围神经系统中。GDNF 可防止 MN 在体内发育过程中发生凋亡，减少运动神经病和变性动物模型中 MN 的损失，使 MN 免受轴索切断术诱导的细胞死亡的影响，并保护 MN 免受慢性变性。脑内 GDNF 给药对黑质纹状体多巴胺系统具有保护和修复作用，这可能对帕金森病新治疗策略的开发具有影响^[1][2]。

Recombinant rat GDNF (5 ng/mL) promotes neurite outgrowth from cultured adult rat dorsal root ganglia (DRG) neurons, and significantly increases the number of IB4-binding neurons and the relative protein expression of galectin-1 in the neuron-enriched culture of DRG^[3].

Recombinant human GDNF (15 and 3 μg; two doses) into the rat striatum (total volume of 1 μL for 2 min; the infusion rate was .5 μl/min) by convection-enhanced delivery (CED). GDNF results in a sharp increase in striatal GDNF levels followed by a rapid decrease between day 3 and 7. Dopamine (DA) turnover is significantly increased in a dose-dependent manner for more than 7 days after a single GDNF infusion^[4].

1.Measured in a cell proliferation assay using SH-SY5Y human neuroblastoma cells. The ED₅₀ is typically ≤50 ng/mL in the presence of Rat GFR alpha-1/GDNF R alpha-1 His Chimera.
2. Immobilized GDNF Protein, Rat (sf9, His) at 10 μg/mL (100 μl/well) can bind rat GFRA1-Fc and the EC₅₀ is 20-46.6 ng/mL.

Rat

Sf9 insect cells

N-6*His

Q07731-1 (S78-I211)

25453  [NCBI]

SPDKQAAALPRRERNRQAAAASPENSRGKGRRGQRGKNRGCVLTAIHLNVTDLGLGYETKEELIFRYCSGSCEAAETMYDKILKNLSRSRRLTSDKVGQACCRPVAFDDDLSFLDDSLVYHILRKHSAKRCGCI

Approximately 20 kDa

Greater than 95% as determined by reducing SDS-PAGE

无菌粉末.

Lyophilized from a 0.2 μm filtered solution of 20 mM Tris, 500 mM NaCl, pH 7.4. Normally 5 % - 8 % trehalose, mannitol and 0.01% Tween 80 are added as protectants before lyophilization.

<1 EU/μg, determined by LAL method.

It is not recommended to reconstitute to a concentration less than 100 μg/mL in ddH₂O.

Stored at -20°C for 2 years. After reconstitution, it is stable at 4°C for 1 week or -20°C for longer (with carrier protein). It is recommended to freeze aliquots at -20°C or -80°C for extended storage.

Room temperature in continental US; may vary elsewhere.

• [1]. Alberto F Cintrón-Colón, et al. GDNF synthesis, signaling, and retrograde transport in motor neurons. Cell Tissue Res. 2020 Oct;382(1):47-56.  [Content Brief]

  [2]. Tomac A, et al. Protection and repair of the nigrostriatal dopaminergic system by GDNF in vivo. Nature.1995;373 (6512): 335-339.  [Content Brief]

  [3]. Shizuka Takaku, et al. GDNF promotes neurite outgrowth and upregulates galectin-1 through the RET/PI3K signaling in cultured adult rat dorsal root ganglion neurons. Neurochem Int. 2013 Feb;62(3):330-9.  [Content Brief]

  [4]. Piotr Hadaczek, et al. Pharmacokinetics and bioactivity of glial cell line-derived factor (GDNF) and neurturin (NTN) infused into the rat brain. Neuropharmacology. 2010 Jun;58(7):1114-21.  [Content Brief]