Aberrant Membranes and Double-Membrane Structures Accumulate in the Axons of Atg5-Null Purkinje Cells before Neuronal Death
Open accessAbstract
Autophagy (macroautophagy) is an evolutionally conserved process by which cytoplasmic proteins and organelles are surrounded by unique double membranes and are subsequently degraded upon fusion with lysosomes. Many autophagy-related genes (Atg) have been identified in yeast; a ubiquitin-like Atg12-Atg5 system is also essential for the elongation of the isolation membrane in mammalian cells. Nevertheless, the regulation of autophagy in neurons remains largely unknown. In this study, we crossed conditional knockout mice Atg5(flox/flox) with pcp2-Cre transgenic mice, which express Cre recombinase through a Purkinje cell-specific promoter, pcp2. In Atg5(flox/flox); pcp2-Cre mice, the Atg5 gene was excised as early as postnatal day 6; Purkinje cells started to degenerate after approximately 8 weeks, and the animals showed an ataxic gait from around 10 months. Initially, however, the Purkinje cells showed axonal swelling around its terminals from as early as 4 weeks after birth. An electron microscopic analysis revealed the accumulation of autophagosome-like double-membrane structures in the swollen regions, together with numerous membranous organelles, such as tubular or sheet-like smooth endoplasmic reticulum and vesicles. These results suggest that Atg5 plays important roles in the maintenance of axon morphology and membrane structures, and its loss of function leads to the swelling of axons, followed by progressive neurodegeneration in mammalian neurons.
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Purkinje cells lacking the essential autophagy genes Atg5 or Atg7 die over time.
“Interestingly, Purkinje cells lacking the essential autophagy genes Atg5 or Atg7 die over time2021.”
From Clec16a is Critical for Autolysosome Function and Purkinje Cell Survival (2016) · cites this paper as [21]
The section ‘Deletion of Atg5 in Purkinje cells caused progressive and cell-autonomous neurodegeneration’ reports that Atg5-deficient Purkinje cells began to be lost about eight weeks after birth. The paper also reports progressive neurodegeneration in mice with Atg7 deleted broadly in neural cells, but our copy does not establish that Atg7-deficient Purkinje cells specifically die over time. The passages have no page numbers in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredAxons in the deep cerebellar nuclei of mice lacking Atg5 and Atg7 in Purkinje cells displayed increased membranous and vacuole-like structures.
“axons in the deep cerebellar nuclei of mice lacking Atg5 and Atg7 in Purkinje cells displayed increased membranous and vacuole-like structures”
From Clec16a is Critical for Autolysosome Function and Purkinje Cell Survival (2016) · cites this paper as [21]
The ‘Aberrant membranous structures and autophagosome-like organelles’ section reports swollen axons in the deep cerebellar nuclei of mice with Purkinje-cell-specific Atg5 deletion; Figure 4 describes frequent aberrant membranes and autophagosome-like organelles in those axons. The paper does not report this finding for Purkinje-cell-specific Atg7 deletion. Its Introduction mentions Atg7 in other knockout contexts, not in this experiment. (LLM, conf=0.90)
Experimental — accuracy not yet measuredConditional deletion of the autophagy genes Atg5 or Atg7 in Purkinje cells leads to degeneration of these cells.
“For example, the conditional deletion of the autophagy genes Atg5 or Atg7 in Purkinje cells leads to degeneration of these cells2021.”
From Clec16a is Critical for Autolysosome Function and Purkinje Cell Survival (2016) · cites this paper as [21]
The section “Deletion of Atg5 in Purkinje cells caused progressive and cell-autonomous neurodegeneration” reports that Purkinje-cell-specific Atg5 deletion led to cell loss. A discussion passage also reports neurodegeneration and Purkinje-cell axonal swelling in Atg7-deficient mice, but those mice had nestin-Cre deletion across neural cells, not Purkinje-cell-specific deletion. Page numbers are unavailable in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredMice with mutations in the autophagy genes Atg5, Atg7, FIP200 and Epg5 show the importance of autophagy in neurons and their stem cell precursors.
“Mice with mutations in the autophagy genes Atg5, Atg7, FIP200 and Epg5 show the importance of autophagy in neurons and their stem cell precursors20212223.”
From Clec16a is Critical for Autolysosome Function and Purkinje Cell Survival (2016) · cites this paper as [21]
In several in vivo models, neurons, particularly Purkinje cells, require functional autophagy to survive.
“In several in vivo models, neurons, and in particular Purkinje cells, demonstrate a striking requirement for functional autophagy in order to survive.”
From Clec16a is Critical for Autolysosome Function and Purkinje Cell Survival (2016) · cites this paper as [21]
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Cites
Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice
Hara, T., Nakamura, K., Matsui, M., Yamamoto, A., Nakahara, Y., Suzuki-Migishima, R., Yokoyama, M., Mishima, K., Saito, I., Okano, H., et al. (2006) · Nature · doi:10.1038/nature04724 · Cited by 3,882 · see citing works
Self-citationLoss of autophagy in the central nervous system causes neurodegeneration in mice
Komatsu, M., Waguri, S., Chiba, T., Murata, S., Iwata, J.-I., Tanida, I., Ueno, T., Koike, M., Uchiyama, Y., Kominami, E., et al. (2006) · Nature · doi:10.1038/nature04723 · Cited by 3,500 · see citing works
The role of autophagy during the early neonatal starvation period
Kuma, A., Hatano, M., Matsui, M., Yamamoto, A., Nakaya, H., Yoshimori, T., Ohsumi, Y., Tokuhisa, T., & Mizushima, N. (2004) · Nature · doi:10.1038/nature03029 · Cited by 2,865 · see citing works
Self-citationImpairment of starvation-induced and constitutive autophagy in <i>Atg7</i> -deficient mice
Komatsu, M., Waguri, S., Ueno, T., Iwata, J., Murata, S., Tanida, I., Ezaki, J., Mizushima, N., Ohsumi, Y., Uchiyama, Y., et al. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200412022 · Cited by 2,331 · see citing works
Self-citationA ubiquitin-like system mediates protein lipidation
Ichimura, Y., Kirisako, T., Takao, T., Satomi, Y., Shimonishi, Y., Ishihara, N., Mizushima, N., Tanida, I., Kominami, E., Ohsumi, M., et al. (2000) · Nature · doi:10.1038/35044114 · Cited by 2,064 · see citing works
Self-citationPreparation of PCR-Quality Mouse Genomic DNA with Hot Sodium Hydroxide and Tris (HotSHOT)
Truett, G. E., Heeger, P. S., Mynatt, R. L., Truett, A. A., Walker, J. A., & Warman, M. L. (2000) · BioTechniques · doi:10.2144/00291bm09 · Cited by 1,748 · see citing works
Dissection of Autophagosome Formation Using Apg5-Deficient Mouse Embryonic Stem Cells
Mizushima, N., Yamamoto, A., Hatano, M., Kobayashi, Y., Kabeya, Y., Suzuki, K., Tokuhisa, T., Ohsumi, Y., & Yoshimori, T. (2001) · The Journal of Cell Biology · doi:10.1083/jcb.152.4.657 · Cited by 1,361 · see citing works
Self-citationA Unified Nomenclature for Yeast Autophagy-Related Genes
Klionsky, D. J., Cregg, J. M., Dunn, W. A., Emr, S. D., Sakai, Y., Sandoval, I. V., Sibirny, A. А., Subramani, S. E., Thumm, M., Marten Veenhuis, A., et al. (2003) · Developmental Cell · doi:10.1016/s1534-5807(03)00296-x · Cited by 1,267 · see citing works
Nakatogawa, H., Ichimura, Y., & Ohsumi, Y. (2007) · Cell · doi:10.1016/j.cell.2007.05.021 · Cited by 1,215 · see citing works
Axon degeneration mechanisms: Commonality amid diversity
Coleman, M. (2005) · Nature reviews. Neuroscience · doi:10.1038/nrn1788 · Cited by 819 · see citing works
Widespread recombinase expression using FLPeR (Flipper) mice
Farley, F. W., Soriano, P. M., Steffen, L. S., & Dymecki, S. M. (2000) · genesis · doi:10.1002/1526-968x(200011/12)28:3/4 · Cited by 602 · see citing works
Autophagy in the Eukaryotic Cell
Reggiori, F., & Klionsky, D. J. (2002) · Eukaryotic Cell · doi:10.1128/ec.01.1.11-21.2002 · Cited by 551 · see citing works
Induction of Autophagy in Axonal Dystrophy and Degeneration
Wang, Q. J., Ding, Y., Kohtz, S., Mizushima, N., Cristea, I. M., Rout, M. P., Chait, B. T., Zhong, Y., Heintz, N., & Yue, Z. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.2261-06.2006 · Cited by 308 · see citing works
Self-citationHollenbeck, P. J. (1993) · The Journal of Cell Biology · doi:10.1083/jcb.121.2.305 · Cited by 295 · see citing works
Ultrastructural neuronal pathology in transgenic mice expressing mutant (P301L) human tau
Lin, W.-L., Lewis, J. M., Yen, S.-H. C., Hutton, M. L., & Dickson, D. W. (2003) · Journal of Neurocytology · doi:10.1023/b:neur.0000021904.61387.95 · Cited by 125 · see citing works
Dumesnil-Bousez, N., & Sotelo, C. (1992) · Journal of Neurocytology · doi:10.1007/bf01186954 · Cited by 93 · see citing works
Bowman, A. B., Lam, Y. C., Jafar-Nejad, P., Chen, H.-K., Richman, R., Samaco, R. C., Fryer, J. D., Kahle, J. J., Orr, H. T., & Zoghbi, H. Y. (2007) · Nature Genetics · doi:10.1038/ng1977 · Cited by 86 · see citing works
Reggiori, F. (2006) · Current topics in developmental biology/Current Topics in Developmental Biology · doi:10.1016/s0070-2153(06)74001-7 · Cited by 85 · see citing works
Tomomura, M., Rice, D. S., Morgan, J. I., & Yuzaki, M. (2001) · European Journal of Neuroscience · doi:10.1046/j.0953-816x.2001.01624.x · Cited by 81 · see citing works
Self-citationThe Lurcher mouse: Fresh insights from an old mutant
Vogel, M. W., Caston, J., Yuzaki, M., & Mariani, J. (2006) · Brain Research · doi:10.1016/j.brainres.2005.11.086 · Cited by 75 · see citing works
Self-citationErnst, C., & Christie, B. R. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2005.10.065 · Cited by 40 · see citing works
Yamamoto, A., Otsu, H., Yoshimori, T., Maeda, N., Mikoshiba, K., & Tashiro, Y. (1991) · Cell Structure and Function · doi:10.1247/csf.16.419 · Cited by 37 · see citing works
Ohara, S. (2004) · Experimental Neurology · doi:10.1016/j.expneurol.2004.03.002 · Cited by 35 · see citing works
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Research works printed but not linked: 1
- Barski JJ, Dethleffsen K, Meyer M. Cre recombinase expression in cerebellar Purkinje cells. Genesis 2000; 28:93-8.
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Sorted by citations
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Mizushima, N., & Komatsu, M. (2011) · Cell · doi:10.1016/j.cell.2011.10.026 · Cited by 6,467 · see citing works
Self-citationMethods in Mammalian Autophagy Research
Mizushima, N., Yoshimori, T., & Levine, B. (2010) · Cell · doi:10.1016/j.cell.2010.01.028 · Cited by 4,497 · see citing works
Self-citationAutophagy in mammalian development and differentiation
Mizushima, N., & Levine, B. (2010) · Nature Cell Biology · doi:10.1038/ncb0910-823 · Cited by 1,555 · see citing works
Self-citationAutophagy and Neurodegeneration: Pathogenic Mechanisms and Therapeutic Opportunities
Menzies, F. M., Fleming, A., Caricasole, A., Bento, C. F., Andrews, S. P., Ashkenazi, A., Füllgrabe, J., Jackson, A., Jimenez Sanchez, M., Karabiyik, C., et al. (2017) · Neuron · doi:10.1016/j.neuron.2017.01.022 · Cited by 1,134 · see citing works
Physiological significance of selective degradation of p62 by autophagy
Komatsu, M., & Ichimura, Y. (2010) · FEBS Letters · doi:10.1016/j.febslet.2010.02.017 · Cited by 516 · see citing works
Sou, Y., Waguri, S., Iwata, J.-I., Ueno, T., Fujimura, T., Hara, T., Sawada, N., Yamada, A., Mizushima, N., Uchiyama, Y., et al. (2008) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-03-0309 · Cited by 475 · see citing works
Self-citationAutophagy and the cell biology of age-related disease
Leidal, A. M., Levine, B., & Debnath, J. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0235-8 · Cited by 424 · see citing works
Autophagy in lysosomal storage disorders
Lieberman, A. P., Puertollano, R., Raben, N., Slaugenhaupt, S., Walkley, S. U., & Ballabio, A. (2012) · Autophagy · doi:10.4161/auto.19469 · Cited by 399 · see citing works
Noncanonical autophagy promotes the visual cycle
Kim, J.-Y., Zhao, H., Martinez, J., Doggett, T. A., Kolesnikov, A. V., Tang, P. H., Ablonczy, Z., Chan, C.-C., Zhou, Z., Green, D. R., et al. (2013) · Cell · doi:10.1016/j.cell.2013.06.012 · Cited by 347 · see citing works
Hale, A. N., Ledbetter, D., Gawriluk, T. R., & Rucker, E. B. (2013) · Autophagy · doi:10.4161/auto.24273 · Cited by 336 · see citing works
Compartment-Specific Regulation of Autophagy in Primary Neurons
Maday, S., & Holzbaur, E. L. F. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.4401-15.2016 · Cited by 309 · see citing works
Friedman, L. G., Lachenmayer, M. L., Wang, J., He, L., Poulose, S. M., Komatsu, M., Holstein, G. R., & Yue, Z. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.5809-11.2012 · Cited by 303 · see citing works
Ye, X., Zhou, S., & Zhang, H. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02334 · Cited by 292 · see citing works
Autophagy plays a critical role in kidney tubule maintenance, aging and ischemia-reperfusion injury
Liu, S., Hartleben, B., Kretz, O., Wiech, T., Igarashi, P., Mizushima, N., Walz, G., & Huber, T. B. (2012) · Autophagy · doi:10.4161/auto.19419 · Cited by 271 · see citing works
Self-citationSenescence, Apoptosis or Autophagy?
Vicencio, J. M., Galluzzi, L., Tajeddine, N., Ortiz, C., Criollo, A., Tasdemir, E., Morselli, E., Younes, A. B., Maiuri, M. C., Lavandero, S., et al. (2008) · Gerontology · doi:10.1159/000129697 · Cited by 259 · see citing works
Physiological Functions of Autophagy
Mizushima, N. (2009) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-00302-8_3 · Cited by 244 · see citing works
Self-citationKuma, A., & Mizushima, N. (2010) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2010.03.002 · Cited by 237 · see citing works
Self-citationMutation in ATG5 reduces autophagy and leads to ataxia with developmental delay
Kim, M., Sandford, E., Gatica, D., Qiu, Y., Liu, X., Zheng, Y., Schulman, B. A., Xu, J., Semple, I., Ro, S.-H., et al. (2016) · eLife · doi:10.7554/elife.12245 · Cited by 225 · see citing works
Autophagy in Neurodegenerative Diseases: A Hunter for Aggregates
Park, H., Kang, J., & Lee, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093369 · Cited by 209 · see citing works
Autophagy for tissue homeostasis and neuroprotection
Mariño, G., Madeo, F., & Kroemer, G. (2011) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2010.10.001 · Cited by 195 · see citing works
Bassoon Controls Presynaptic Autophagy through Atg5
Okerlund, N. D., Schneider, K., Leal‐Ortiz, S., Montenegro‐Venegas, C., Kim, S. A., Garner, L. C., Waites, C. L., Gundelfinger, E. D., Reimer, R. J., & Garner, C. C. (2017) · Neuron · doi:10.1016/j.neuron.2017.01.026 · Cited by 189 · see citing works
Autophagy in Neuroprotection and Neurodegeneration: A Question of Balance
Cherra, S. J., & Chu, C. T. (2008) · Future Neurology · doi:10.2217/14796708.3.3.309 · Cited by 191 · see citing works
The cellular pathways of neuronal autophagy and their implication in neurodegenerative diseases
Yue, Z., Friedman, L. G., Komatsu, M., & Tanaka, K. (2009) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2009.01.016 · Cited by 173 · see citing works
Luo, L., Ambrozkiewicz, M. C., Benseler, F., Chen, C., Dumontier, É., Falkner, S., Furlanis, E., Gomez, A. M., Hoshina, N., Huang, W., et al. (2020) · Neuron · doi:10.1016/j.neuron.2020.01.008 · Cited by 167 · see citing works
Self-citationAll-you-can-eat: autophagy in neurodegeneration and neuroprotection
Jaeger, P. A., & Wyss‐Coray, T. (2009) · Molecular Neurodegeneration · doi:10.1186/1750-1326-4-16 · Cited by 175 · see citing works
Atg5 and Ambra1 differentially modulate neurogenesis in neural stem cells
Vázquez, P., Arroba, A. I., Cecconi, F., de la Rosa, E. J., Boya, P., & De Pablo, F. (2012) · Autophagy · doi:10.4161/auto.8.2.18535 · Cited by 171 · see citing works
Macroautophagy deficiency mediates age-dependent neurodegeneration through a phospho-tau pathway
Inoue, K., Rispoli, J., Kaphzan, H., Klann, E., Chen, E. I., Kim, J., Komatsu, M., & Abeliovich, A. (2012) · Molecular Neurodegeneration · doi:10.1186/1750-1326-7-48 · Cited by 168 · see citing works
Kononenko, N. L., Classen, G. A. E., Kuijpers, M., Puchkov, D., Maritzen, T., Tempes, A., Malik, A. R., Skalecka, A., Bera, S., Jaworski, J., et al. (2017) · Nature Communications · doi:10.1038/ncomms14819 · Cited by 161 · see citing works
Congenital disorders of autophagy: an emerging novel class of inborn errors of neuro-metabolism.
Ebrahimi‐Fakhari, D., Saffari, A., Wahlster, L., Lu, J., Byrne, S., Hoffmann, G., Jungbluth, H., & Şahin, M. (2016) · Brain : a journal of neurology · doi:10.1093/brain/awv371 · Cited by 150 · see citing works
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Park, H.-Y. L., Kim, J. H., & Park, C. (2012) · Cell Death and Disease · doi:10.1038/cddis.2012.26 · Cited by 153 · see citing works
Accumulation of AMPA Receptors in Autophagosomes in Neuronal Axons Lacking Adaptor Protein AP-4
Matsuda, S., Miura, E., Matsuda, K., Kakegawa, W., Kohda, K., Watanabe, M., & Yuzaki, M. (2008) · Neuron · doi:10.1016/j.neuron.2008.02.012 · Cited by 152 · see citing works
Self-citationAutophagy: a multifaceted player in the fate of sperm
Wang, M., Zeng, L., Su, P., Ma, L., Zhang, M., & Zhang, Y. (2021) · Human Reproduction Update · doi:10.1093/humupd/dmab043 · Cited by 153 · see citing works
Autophagy in axonal and dendritic degeneration
Yang, Y., Coleman, M. P., Zhang, L., Zheng, X., & Yue, Z. (2013) · Trends in Neurosciences · doi:10.1016/j.tins.2013.04.001 · Cited by 144 · see citing works
Macroautophagy in CNS health and disease
Griffey, C. J., & Yamamoto, A. (2022) · Nature reviews. Neuroscience · doi:10.1038/s41583-022-00588-3 · Cited by 144 · see citing works
The endoplasmic reticulum and protein trafficking in dendrites and axons
Ramírez, O. A., & Couve, A. (2011) · Trends in Cell Biology · doi:10.1016/j.tcb.2010.12.003 · Cited by 142 · see citing works
Mechanisms of neuronal homeostasis: Autophagy in the axon
Maday, S. (2016) · Brain Research · doi:10.1016/j.brainres.2016.03.047 · Cited by 123 · see citing works
Neuronal autophagy and intercellular regulation of homeostasis in the brain
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ATG5: A central autophagy regulator implicated in various human diseases
Changotra, H., Kaur, S., Yadav, S. S., Gupta, G. L., Parkash, J., & Duseja, A. K. (2022) · Cell Biochemistry and Function · doi:10.1002/cbf.3740 · Cited by 117 · see citing works
Reyes, N., Fisher, J. K., Austgen, K., VandenBerg, S. R., Huang, E. J., & Oakes, S. A. (2010) · Journal of Clinical Investigation · doi:10.1172/jci42986 · Cited by 113 · see citing works
Chakrabarti, L., Eng, J., Ivanov, N., Garden, G. A., & La Spada, A. R. (2009) · Molecular Brain · doi:10.1186/1756-6606-2-24 · Cited by 112 · see citing works
<i>Atg9a</i> deficiency causes axon-specific lesions including neuronal circuit dysgenesis
Yamaguchi, J., Suzuki, C., Nanao, T., Kakuta, S., Ozawa, K., Tanida, I., Saitoh, T., Sunabori, T., Komatsu, M., Tanaka, K., et al. (2018) · Autophagy · doi:10.1080/15548627.2017.1314897 · Cited by 109 · see citing works
The Endolysosomal System and Proteostasis: From Development to Degeneration
Winckler, B., Faúndez, V., Maday, S., Cai, Q., Almeida, C. G., & Zhang, H. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.1665-18.2018 · Cited by 105 · see citing works
Review: Autophagy in neurodegeneration: firefighter and/or incendiarist?
Rami, A. (2009) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2009.01034.x · Cited by 107 · see citing works
Mechanisms of Axonal Spheroid Formation in Central Nervous System Wallerian Degeneration
Beirowski, B., Nógrádi, A., Babetto, E., Garcia-Alias, G., & Coleman, M. P. (2010) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181da84db · Cited by 104 · see citing works
Autophagy in neuronal cells: general principles and physiological and pathological functions
Daμμe, M., Suntio, T., Säftig, P., & Eskelinen, E. (2014) · Acta Neuropathologica · doi:10.1007/s00401-014-1361-4 · Cited by 102 · see citing works
The emerging roles of protein homeostasis‐governing pathways in Alzheimer's disease
Cheng, J., North, B. J., Zhang, T., Dai, X., Tao, K., Guo, J., & Wei, W. (2018) · Aging Cell · doi:10.1111/acel.12801 · Cited by 96 · see citing works
Ivankovic, D., Drew, J., Lesept, F., White, I. J., López‐Doménech, G., Tooze, S. A., & Kittler, J. T. (2019) · Autophagy · doi:10.1080/15548627.2019.1615302 · Cited by 83 · see citing works
Neuronal Autophagy as a Mediator of Life and Death
Puyal, J., Ginet, V., Grishchuk, Y., Truttmann, A. C., & Clarke, P. G. H. (2011) · The Neuroscientist · doi:10.1177/1073858411404948 · Cited by 84 · see citing works
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Rogers, R. S., Tungtur, S., Tanaka, T., Nadeau, L. L., Badawi, Y., Wang, H., Ni, H.-M., Ding, W.-X., & Nishimune, H. (2017) · Frontiers in Neuroscience · doi:10.3389/fnins.2017.00473 · Cited by 83 · see citing works
The Crucial Role of Atg5 in Cortical Neurogenesis During Early Brain Development
Lv, X., Jiang, H., Li, B., Liang, Q., Wang, S., Zhao, Q., & Jiao, J. (2014) · Scientific Reports · doi:10.1038/srep06010 · Cited by 83 · see citing works
Selective autophagy as a therapeutic target for neurological diseases
Xu, W., Ocak, U., Gao, L., Tu, S., Lenahan, C., Zhang, J., & Shao, A. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03667-9 · Cited by 82 · see citing works
Autophagy supports survival and phototransduction protein levels in rod photoreceptors
Zhou, Z., Doggett, T. A., Sène, A., Apte, R. S., & Ferguson, T. A. (2015) · Cell Death and Differentiation · doi:10.1038/cdd.2014.229 · Cited by 78 · see citing works
Differential regulation of autophagy during metabolic stress in astrocytes and neurons
Kulkarni, A., Dong, A., Kulkarni, V. V., Chen, J., Laxton, O., Anand, A., & Maday, S. (2019) · Autophagy · doi:10.1080/15548627.2019.1703354 · Cited by 77 · see citing works
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Compartment‐specific dynamics and functions of autophagy in neurons
Kulkarni, V. V., & Maday, S. (2017) · Developmental Neurobiology · doi:10.1002/dneu.22562 · Cited by 72 · see citing works
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Zhao, Y. G., Zhao, H., Miao, L., Wang, L., Sun, F., & Zhang, H. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.415968 · Cited by 72 · see citing works
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Tomoda, T., Yang, K., & Sawa, A. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.07.018 · Cited by 71 · see citing works
Su, L., Luo, R., Liu, Q., Su, J.-R., Yang, L.-X., Ding, Y., Xu, L., & Yao, Y. (2017) · Autophagy · doi:10.1080/15548627.2017.1332549 · Cited by 72 · see citing works
Autophagy in the Regulation of Tissue Differentiation and Homeostasis
Perrotta, C., Cattaneo, M. G., Molteni, R., & Palma, C. D. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.602901 · Cited by 72 · see citing works
SETX (senataxin), the helicase mutated in AOA2 and ALS4, functions in autophagy regulation
Richard, P., Feng, S., Tsai, Y.-L., Li, W., Rinchetti, P., Muhith, U., Irizarry-Cole, J., Stolz, K., Sanz, L. A., Hartono, S. R., et al. (2020) · Autophagy · doi:10.1080/15548627.2020.1796292 · Cited by 68 · see citing works
Autophagy dysfunction in neuropathic pain
Liu, X., Zhu, M., Ju, Y., Li, A., & Sun, X. (2019) · Neuropeptides · doi:10.1016/j.npep.2019.03.005 · Cited by 63 · see citing works
Pharmacological modulation of autophagy for Alzheimer's disease therapy: Opportunities and obstacles
Deng, Z., Dong, Y., Zhou, X., Lu, J.-H., & Yue, Z. (2022) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.12.009 · Cited by 58 · see citing works
Synaptic activity controls autophagic vacuole motility and function in dendrites
Kulkarni, V. V., Anand, A., Herr, J. B., Miranda, C., Vogel, M. C., & Maday, S. (2021) · The Journal of Cell Biology · doi:10.1083/jcb.202002084 · Cited by 59 · see citing works
Deregulation of autophagy and vesicle trafficking in Parkinson’s disease
Sheehan, P., & Yue, Z. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.04.013 · Cited by 57 · see citing works
Sorafenib-induced defective autophagy promotes cell death by necroptosis
Kharaziha, P., Chioureas, D., Baltatzis, G., Fonseca, P., Rodriguez, P. Q., Gogvadze, V. G., Lennartsson, L., Björklund, A.-C., Zhivotovsky, B., Grandér, D., et al. (2015) · Oncotarget · doi:10.18632/oncotarget.5797 · Cited by 56 · see citing works
Piras, A., Schiaffino, L., Boido, M., Valsecchi, V., Guglielmotto, M., Amicis, E. D., Puyal, J., Garcerá, A., Tamagno, E., Soler, R. M., et al. (2017) · Cell Death and Disease · doi:10.1038/s41419-017-0086-4 · Cited by 58 · see citing works
Dysfunctional autophagy in Alzheimer’s disease: pathogenic roles and therapeutic implications
Liang, J., & Jia, J. (2014) · Neuroscience Bulletin · doi:10.1007/s12264-013-1418-8 · Cited by 50 · see citing works
Pathophysiological Role of Autophagy: Lesson from Autophagy-Deficient Mouse Models
Ichimura, Y., & Komatsu, M. (2011) · EXPERIMENTAL ANIMALS · doi:10.1538/expanim.60.329 · Cited by 48 · see citing works
Assessment of Autophagy in Neurons and Brain Tissue
Benito‐Cuesta, I., Díez, H., Ordóñez‐Gutiérrez, L., & Wandosell, F. G. (2017) · Cells · doi:10.3390/cells6030025 · Cited by 49 · see citing works
Wignes, J. A., Goldman, J. W., Weihl, C. C., Bartley, M. G., & Andley, U. P. (2013) · Experimental Eye Research · doi:10.1016/j.exer.2013.06.026 · Cited by 48 · see citing works
Autophagy dysregulation in cell culture and animals models of spinal muscular atrophy
Custer, S. K., & Androphy, E. J. (2014) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2014.06.006 · Cited by 49 · see citing works
Atg9A Protein, an Autophagy-related Membrane Protein, Is Localized in the Neurons of Mouse Brains
Tamura, H., Shibata, M., Koike, M., Sasaki, M., & Uchiyama, Y. (2010) · Journal of Histochemistry & Cytochemistry · doi:10.1369/jhc.2010.955690 · Cited by 49 · see citing works
A novel and functional variant within the ATG5 gene promoter in sporadic Parkinson's disease
Chen, D., Zhu, C., Wang, X., Feng, X., Pang, S., Huang, W., Hawley, R. G., & Yan, B. (2013) · Neuroscience Letters · doi:10.1016/j.neulet.2013.01.044 · Cited by 46 · see citing works
Novel insights into the clinical and molecular spectrum of congenital disorders of autophagy
Teinert, J., Behne, R., Wimmer, M., & Ebrahimi‐Fakhari, D. (2019) · Journal of Inherited Metabolic Disease · doi:10.1002/jimd.12084 · Cited by 46 · see citing works
Organization of the autophagy pathway in neurons
Sidibe, D. K., Vogel, M. C., & Maday, S. (2022) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2022.102554 · Cited by 38 · see citing works
Feng, F., Zhang, M., Yang, C., Heng, X., & Wu, X. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.109441 · Cited by 42 · see citing works
Minis, A., Rodriguez, J. A., Levin, A., Liu, K., Govek, E., Hatten, M. E., & Steller, H. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1911921116 · Cited by 40 · see citing works
Molecular Mechanism and Regulation of Autophagy and Its Potential Role in Epilepsy
Zhu, H., Wang, W., & Li, Y. (2022) · Cells · doi:10.3390/cells11172621 · Cited by 41 · see citing works
Histopathological and Neurological Features of Atg4b Knockout Mice
Read, R., Savelieva, K. V., Baker, K. B., Hansen, G. M., & Vogel, P. (2010) · Veterinary Pathology · doi:10.1177/0300985810375810 · Cited by 38 · see citing works
The Interplay of HIV and Autophagy in Early Infection
Cabrera-Rodríguez, R., Pérez-Yanes, S., Estévez‐Herrera, J., Márquez-Arce, D., Cabrera, C., Espert, L., Blanco, J., & Valenzuela-Fernández, A. (2021) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.661446 · Cited by 36 · see citing works
A Variant of the Autophagy-Related 5 Gene Is Associated with Child Cerebral Palsy
Xu, J., Xia, L., Shang, Q., Du, J., Zhu, D., Wang, Y., Bi, D., Song, J., Ma, C., Gao, C., et al. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00407 · Cited by 34 · see citing works
Modulating Macroautophagy: A Neuronal Perspective
Johnson, C. W., Melia, T. J., & Yamamoto, A. (2012) · Future Medicinal Chemistry · doi:10.4155/fmc.12.112 · Cited by 31 · see citing works
The HERC2 ubiquitin ligase is essential for embryonic development and regulates motor coordination
Cubillos‐Rojas, M., Schneider, T., Hadjebi, O., Pedrazza, L., de Oliveira, J. R., Vives, F. L., Guénet, J., Duran, J., de Anta, J. M., Alcántara, S., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.11270 · Cited by 32 · see citing works
Autophagy in α-Synucleinopathies—An Overstrained System
Fellner, L., Gabassi, E., Haybaeck, J., & Edenhofer, F. (2021) · Cells · doi:10.3390/cells10113143 · Cited by 33 · see citing works
Nishiyama, J., Matsuda, K., Kakegawa, W., Yamada, N., Motohashi, J., Mizushima, N., & Yuzaki, M. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.6030-09.2010 · Cited by 33 · see citing works
Self-citationCrosstalk between presynaptic trafficking and autophagy in Parkinson's disease
Pan, P., Zhu, Y., Shen, Y., & Yue, Z. (2018) · Neurobiology of Disease · doi:10.1016/j.nbd.2018.04.020 · Cited by 31 · see citing works
Does autophagy work in synaptic plasticity and memory?
Shehata, M. H., & Inokuchi, K. (2014) · Reviews in the Neurosciences · doi:10.1515/revneuro-2014-0002 · Cited by 32 · see citing works
Clec16a is Critical for Autolysosome Function and Purkinje Cell Survival
Redmann, V., Lamb, C. A., Hwang, S., Orchard, R. C., Kim, S., Razi, M., Milam, A., Park, S., Yokoyama, C. C., Kambal, A., et al. (2016) · Scientific Reports · doi:10.1038/srep23326 · Cited by 31 · see citing works
Autophagy and lysosomal pathways in nervous system disorders
Bingol, B. (2018) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2018.04.009 · Cited by 31 · see citing works
The axonal endoplasmic reticulum and protein trafficking: Cellular bootlegging south of the soma
Gonzalez‐Silva, C., & Couve, A. (2013) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2013.12.004 · Cited by 31 · see citing works
Emerging roles of ATG9/ATG9A in autophagy: implications for cell and neurobiology
Choi, J., Jang, H., Xuan, Z., & Park, D. (2024) · Autophagy · doi:10.1080/15548627.2024.2384349 · Cited by 28 · see citing works
Stress and signaling pathways regulating autophagy: From behavioral models to psychiatric disorders
Pierone, B. C., Pereira, C. A., Garcez, M. L., & Kaster, M. P. (2020) · Experimental Neurology · doi:10.1016/j.expneurol.2020.113485 · Cited by 29 · see citing works
Sano, T., Kohyama‐Koganeya, A., Kinoshita, M. O., Tatsukawa, T., Shimizu, C., Oshima, E., Yamada, K., Le, T. D., Akagi, T., Tohyama, K., et al. (2018) · Neuroscience Research · doi:10.1016/j.neures.2018.02.006 · Cited by 29 · see citing works
Endogenous Mechanisms of Neuroprotection: To Boost or Not to Be
Marmolejo-Martínez-Artesero, S., Casas, C., & Romeo-Guitart, D. (2021) · Cells · doi:10.3390/cells10020370 · Cited by 27 · see citing works
MMP-2 mediates Purkinje cell morphogenesis and spine development in the mouse cerebellum
Verslegers, M., Hove, I. V., Dekeyster, E., Gantois, I., Hu, T., D’Hooge, R., Arckens, L., & Moons, L. (2014) · Brain Structure and Function · doi:10.1007/s00429-014-0747-3 · Cited by 27 · see citing works
Reserve Autophagic Capacity in Alveolar Epithelia Provides a Replicative Niche for Influenza A Virus
Hahn, D., Na, C.-L., & Weaver, T. E. (2014) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2013-0437oc · Cited by 24 · see citing works
Santarelli, S., Londero, C., Soldano, A., Candelaresi, C., Todeschini, L., Vernizzi, L., & Bellosta, P. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2023.1082047 · Cited by 23 · see citing works
Inoue, K., Rispoli, J. M., Yang, L., MacLeod, D., Beal, M. F., Klann, E., & Abeliovich, A. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003845 · Cited by 22 · see citing works
Compensatory increases of select proteostasis networks after Hsp70 inhibition in cancer cells
Sannino, S., Guerriero, C. J., Sabnis, A. J., Stolz, D. B., Wallace, C. T., Wipf, P., Watkins, S. C., Bivona, T. G., & Brodsky, J. L. (2018) · Journal of Cell Science · doi:10.1242/jcs.217760 · Cited by 23 · see citing works
- Authors
- Nishiyama, J., Miura, E., Mizushima, N., Watanabe, M., & Yuzaki, M.
- Affiliations
- Keio University (JP)
- Hokkaido University (JP)
- Tokyo Medical and Dental University (JP)
- Venue
- Autophagy
- Publisher
- Informa UK Limited
- Published
- 2007-11-26
- Volume
- 3
- Issue
- 6
- Pages
- 591-596
- ISSN
- 1554-8627 (ISSN-L)
- 1554-8635
- OpenAlex
- W2000936337
- Cited by
- 159
- References
- 23
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 6 · 2023: 6 · 2022: 7 · 2021: 15 · 2020: 10 · 2019: 13 · 2018: 14 · 2017: 12 · 2016: 6 · 2015: 5 · 2014: 10 · 2013: 11 · 2012: 11
- FWCI
- 4.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Autophagy (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Genetic Neurodegenerative Diseases
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- ATG5, Purkinje cells, axonal swellings, axonal degeneration, neuronal cell death, neurodegeneration, cerebellar ataxia, smooth endoplasmic reticulum
- MeSH terms
- Autophagy-Related Protein 5, Animals, Axons, Cell Membrane, Microtubule-Associated Proteins, Neurons, Purkinje Cells, Cell Death, Gene Deletion, Mice, Knockout, Cell Shape, Mice
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