Measurement of autophagy flux in the nervous system in vivo

被引：96

作者：

Castillo, K. ^{[1
,2
]}

Valenzuela, V. ^{[1
,2
]}

Matus, S. ^{[3
]}

Nassif, M. ^{[1
,2
]}

Onate, M. ^{[1
,2
]}

Fuentealba, Y. ^{[1
,2
]}

Encina, G. ^{[1
,2
]}

Irrazabal, T. ^{[1
,2
]}

Parsons, G. ^{[4
]}

Court, F. A. ^{[3
,5
]}

Schneider, B. L. ^{[6
]}

Armentano, D. ^{[4
]}

Hetz, C. ^{[1
,2
,3
,7
]}

机构：

[1] Univ Chile, Fac Med, Inst Biomed Sci, Santiago 7, Chile

[2] Univ Chile, Inst Biomed Sci, Program Cellular & Mol Biol, Ctr Mol Studies Cell, Santiago, Chile

[3] Neuroun Biomed Fdn, Santiago, Chile

[4] Genzyme Corp, Dept Mol Biol, Framingham, MA 01701 USA

[5] Pontificia Univ Catolica Chile, Fac Biol, Millennium Nucleus Regenerat Biol, Santiago, Chile

[6] Ecole Polytech Fed Lausanne, Brain Mind Inst, Neurodegenerat Studies Lab, Lausanne, Switzerland

[7] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA

来源：

CELL DEATH & DISEASE | 2013年 / 4卷

基金：

瑞士国家科学基金会;

关键词：

Autophagy; adeno-associated vector (AAV); microtubule-associated protein 1 light chain 3 (LC3); nervous system; autophagy flux; SPINAL-CORD-INJURY; MOUSE MODEL; AXONAL DEGENERATION; DISEASE; RAPAMYCIN; BRAIN; TREHALOSE; TRANSPORT; CELLS; MICE;

D O I：

10.1038/cddis.2013.421

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Accurate methods to measure autophagic activity in vivo in neurons are not available, and most of the studies are based on correlative and static measurements of autophagy markers, leading to conflicting interpretations. Autophagy is an essential homeostatic process involved in the degradation of diverse cellular components including organelles and protein aggregates. Autophagy impairment is emerging as a relevant factor driving neurodegeneration in many diseases. Moreover, strategies to modulate autophagy have been shown to provide protection against neurodegeneration. Here we describe a novel and simple strategy to express an autophagy flux reporter in the nervous system of adult animals by the intraventricular delivery of adeno-associated viruses (AAV) into newborn mice. Using this approach we efficiently expressed a monomeric tandem mCherry-GFP-LC3 construct in neurons of the peripheral and central nervous system, allowing the measurement of autophagy activity in pharmacological and disease settings.

引用

页码：e917 / e917

页数：11

共 48 条

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