生物谷报道：日本研究人员28日发表报告说，动物实验表明，顽固性哮喘可能是由免疫细胞产生异常免疫反应引起的。
日本兵库医科大学、佐贺大学、大阪大学研究人员组成的研究小组在28日的美国《国家科学院学报》网络版上发表论文说，他们向实验鼠的咽喉部位注射毒素，使其咽喉产生炎症，分析实验鼠体内的反应。结果发现，炎症部位分泌的物质可对一种淋巴细胞发挥作用，引起异常免疫反应，从而导致呼吸困难和支气管炎。
随着这种免疫反应反复发生，实验鼠的哮喘症状也逐步恶化。研究人员同时确认，抑制炎症部位分泌的物质发挥作用，哮喘症状就会消失。
研究人员推测，成人顽固性哮喘可能也是其自身产生的炎症物质在作怪。参与研究的兵库医科大学教授中西宪司说，这项成果解释了成人哮喘恶化的机制。研究人员下一步计划利用大型动物进行类似实验。（新华网）
原始出处:
Published online before print August 28, 2007
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0701311104
Neuroscience
Essential role for autophagy protein Atg7 in the maintenance of axonal homeostasis and the prevention of axonal degeneration
( axon | axonopathy | neurodegeneration | autophagosome | Purkinje cell )
Masaaki Komatsu *, Qing Jun Wang ¶, Gay R. Holstein ¶, Victo
r L. Friedrich Jr. ¶, Jun-ichi Iwata *, Eiki Kominami , Brian T. Chait , Keiji Tanaka *, and Zhenyu Yue ¶||
¶Departments of Neurology and Neuroscience, Mount Sinai School of Medicine, New York, NY 10029; *Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 113-8613, Japan; Department of Biochemistry, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan; Precursory Research for Embryonic Science and Technology, Japan Science and Technology Corporation, Kawaguchi 332-0012, Japan; and Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, Rockefeller University, New York, NY 10065
Edited by Pietro V. De Camilli, Yale University School of Medicine, New Haven, CT, and approved July 19, 2007 (received for review February 14, 2007)
Autophagy is a regulated lysosomal degradation process that involves autophagosome formation and transport. Although recent evidence indicates that basal levels of autophagy protect against neurodegeneration, the exact mechanism whereby this occurs is not known. By using conditional knockout mutant mice, we report that neuronal autophagy is particularly important for the maintenance of local homeostasis of axon terminals and protection against axonal degeneration. We show that specific ablation of an essential autophagy gene, Atg7, in Purkinje cells initially causes cell-autonomous, progressive dystrophy (manifested by axonal swellings) and degeneration of the axon terminals. Consistent with suppression of autophagy, no autophagosomes are observed in these dystrophic swellings, which is in contrast to accumulation of autophagosomes in the axonal dystrophic swellings under pathological conditions. Axonal dystrophy of mutant Purkinje cells proceeds with little sign of dendritic or spine atrophy, indicating that axon terminals are much more vulnerable to autophagy impairment than dendrites. This early pathological event in the axons is followed by cell-autonomous Purkinje cell death and mouse behavioral deficits. Furthermore, ultrastructural analyses of mutant Purkinje cells reveal an accumulation of aberrant membrane structures in the axonal dystrophic swellings. Finally, we observe double-membrane vacuole-like structures in wild-type Purkinje cell axons, whereas these structures are abolished in mutant Purkinje cell axons. Thus, we conclude that the autophagy protein Atg7 is required for membrane trafficking and turnover in the axons. Our study implicates impairment of axonal autophagy as a possible mechanism for axonopathy associated with neurodegeneration.
