2019.08.05 周一

激活自噬的小分子能刺激头发生长

Cell Reports (IF:7.815, 1区)

编译：周华璐

研究背景

头发扮演着重要的角色，从保持体温到保持心理健康。脱发或秃头影响着全球数百万人，但目前缺乏可用于头发再生的方法。

研究方法

首先，作者测试α-KG是否能增加头发再生,使用常用的体内C57BL/6j小鼠背皮肤模型。由于用雷帕霉素可引起自噬，因此，作者想知道雷帕霉素是否也能促进头发再生，并且检测TOR蛋白和AMPK这些与自噬非常相关的信号指标。由于过去的研究表明α-KB也可能有作用，因此本文也检测了其效果。

研究结果

结果表明静止的(休止期)毛囊可以被激活自噬的小分子刺激来启动生长期和头发生长。这些小分子包括代谢物α-酮戊二酸 (α-KG) , α-酮丁酸 (α-KB), 以及会影响mTOR和AMPK信号的处方药：雷帕霉素和二甲双胍。这些药物对头发生长的刺激可以被特定的自噬抑制剂阻断，这表明自噬和头发再生之间存在一种机制上的联系。一致的，在头发从生长期进入自然毛囊周期期间,以及在老年小鼠口服α-KB防止脱发的期间，可以检测到自噬的增加。

研究结论

本文的研究发现，当自然的毛发生长期诱导信号缺失时，生长期可以在休止期中被药物激活，这对脱发患者的治疗有意义。

Chai M, Jiang M, Vergnes L, et al. Stimulation of Hair Growth by Small Molecules that Activate Autophagy[J]. Cell Reports, 2019, 27(12): 3413-3421.

学者简介

Jing Huang

教授 加州大学洛杉矶分校分子和药物药理学系

http://labs.pharmacology.ucla.edu/huanglab/jing.html

Dr. Jing Huang is a professor in the Department of Molecular and Medical Pharmacology at UCLA. She received her B.S. in Genetics from Fudan University in China before coming to the United States for graduate studies. Her Ph.D. in Biochemistry and Molecular Biology was done with the late Hal Weintraub and Larry Kedes, investigating the molecular mechanisms of gene regulation by bHLH transcription factors in cell fate determination and cell differentiation. She was a HHMI postdoctoral fellow in Chemistry and Chemical Biology with Stuart Schreiber, using chemical genetics and functional genomics approaches to study signal transduction and gene expression. Her lab is interested in understanding the logic underlying cellular networks and in developing novel methods and reagents for interrogating molecular and higher-order functions in normal biology and in diseases. A current focus of the lab is on the molecular regulation of longevity and the development of anti-aging drugs that can be used to prevent and/or treat age-related diseases, particularly cancer, heart disease, and neurodegenerative diseases.