PNAS：树皮中一种化学物质能激发脑细胞生长

xielirong

科学家发现树皮中的一种物质能模仿大脑内负责激发神经细胞信号的化学反应。神经细胞信号在脑细胞生长、生存和可塑性方面起着非常重要的作用。

这种被称为gambogic amide（藤黄胺）的物质作用类似大脑中的神经生长因子（NGF）。NGF和神经受体TrkA结合，从而激发神经信号。科学家已经知道TrkA密度的减少和神经萎缩及严重的认知缺陷——例如阿兹海默症等有关。

由于藤黄胺同时还和TrKA结合并激发神经信号，科学家相信这能作为治疗神经退化疾病的潜在手段，例如中风、阿兹海默症和外围糖尿病引起的神经疾病等。研究结果发表在在线版《美国国家科学院院刊》（Proceedings of the National Academy of Sciences，PNAS）上。负责研究的科学家包括Emory大学的病理学和实验医学副教授Keqiang Ye博士、第一作者Sung-Wuk Jang博士，以及Ye实验室的博士后Masashi Okada等等。

藤黄胺来源于藤黄酸，这是藤黄（雌黄）的主要成分。藤黄是来自于东南亚藤黄属植物的一种褐橙色树脂。东南亚地区使用这种胶质物来治疗癌症已经有数千年历史了，并且这一方法对于正常细胞没有任何毒副作用。

Ye表示：“人类会自然产生神经生长因子，它们激发特定类型神经细胞的生长和分化。但当人工合成并用于治疗时NGF的效果和生物效率不佳，而且其制造成本昂贵。”

目前科学家正在进行前期临床测试，以确定身体处理藤黄胺的过程，并确认其是无毒的。
Chemical compound found in tree bark stimulates growth, survival of brain cells
Researchers have identified a compound in tree bark that mimics the chemical reactions of a naturally occurring molecule in the brain responsible for stimulating neuronal cell signaling. Neuronal cell signaling plays a crucial role in the growth, plasticity and survival of brain cells.

The tree bark compound, known as gambogic amide, behaves much like Nerve Growth Factor (NGF), a molecule found in the brain. NGF binds to TrkA, a neuronal receptor, and activates neuronal signaling. It is known that the loss of TrkA density correlates with neuronal atrophy and severe cognitive impairment such as that associated with Alzheimer's disease.

Because gambogic amide also binds to TrKA and activates neuronal signaling, the researchers believe it may have potential as a therapeutic treatment in people affected by neurodegenerative disease, such as stroke, Alzheimer誷 disease and peripheral diabetic neuropathies.

Results of the study are published online in the Proceedings of the National Academy of Sciences and will be published in a future print edition.

The research was conducted by Emory University scientists Keqiang Ye, PhD, associate professor of pathology and laboratory medicine; first author Sung-Wuk Jang, PhD, and Masashi Okada, PhD, post-doctoral fellows in Dr. Ye's lab; Iqbal Sayeed, PhD, instructor; Donald Stein, PhD, Asa G. Candler Professor of Medicine; and Peng Jin, PhD, assistant professor of human genetics; and Dr. Ge Xiao at the Centers for Disease Control and Prevention.

Gambogic amide is derived from gambogic acid, a major ingredient of gamboges, a brownish-orange resin exuded from the Southeast Asian Garcinia hanburryi tree. The resin has been used in that area of the world for thousands of years to treat cancers without any reported toxicity to noncancerous cells.

\"Humans actually have a naturally occurring molecule in the body, Nerve Growth Factor (NGF), which stimulates the growth and differentiation of certain types of nerve cells. However, NGF has poor pharmocokinetics and bioavailability when synthetically manufactured and used therapeutically, and it is also expensive to produce,\" Dr. Ye says.

\"revious research had focused on copying the chemical structure of NGF, but the cyclopeptide mimetics are not potent enough to use as a therapeutic agent. Instead, we decided that we needed to identify a more robust molecule that would pharmacologically mimic NGF's effect on brain cells by binding to TrkA. What we came up with was gambogic amide.\" Dr. Ye says.

The researchers are now conducting further pre-clinical research to investigate how the body processes gambogic amide and to confirm that it is in fact non-toxic.