生物谷報道：日本研究人員28日發(fā)表報告說，動物實驗表明,，頑固性哮喘可能是由免疫細胞產(chǎn)生異常免疫反應引起的。
日本兵庫醫(yī)科大學,、佐賀大學,、大阪大學研究人員組成的研究小組在28日的美國《國家科學院學報》網(wǎng)絡版上發(fā)表論文說，他們向?qū)嶒炇蟮难屎聿课蛔⑸涠舅?，使其咽喉產(chǎn)生炎癥,，分析實驗鼠體內(nèi)的反應。結(jié)果發(fā)現(xiàn),，炎癥部位分泌的物質(zhì)可對一種淋巴細胞發(fā)揮作用,，引起異常免疫反應，從而導致呼吸困難和支氣管炎,。
隨著這種免疫反應反復發(fā)生,，實驗鼠的哮喘癥狀也逐步惡化。研究人員同時確認,，抑制炎癥部位分泌的物質(zhì)發(fā)揮作用,，哮喘癥狀就會消失。
研究人員推測,，成人頑固性哮喘可能也是其自身產(chǎn)生的炎癥物質(zhì)在作怪,。參與研究的兵庫醫(yī)科大學教授中西憲司說,，這項成果解釋了成人哮喘惡化的機制。研究人員下一步計劃利用大型動物進行類似實驗,。（新華網(wǎng)）
原始出處:
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.
