Lysosome trafficking and signaling in health and neurodegenerative diseases
Lysosomes, single-membrane organelles defined by a uniquely strong acidic lumenal pH and high content of acid hydrolases, are the shared degradative compartments of the endocytic and autophagic pathways. These pathways, and especially lysosomes, are points of particular vulnerability in many neurode...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-02-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996118301530 |
| _version_ | 1818352333677920256 |
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| author | Pearl P.Y. Lie Ralph A. Nixon |
| author_facet | Pearl P.Y. Lie Ralph A. Nixon |
| author_sort | Pearl P.Y. Lie |
| collection | DOAJ |
| description | Lysosomes, single-membrane organelles defined by a uniquely strong acidic lumenal pH and high content of acid hydrolases, are the shared degradative compartments of the endocytic and autophagic pathways. These pathways, and especially lysosomes, are points of particular vulnerability in many neurodegenerative diseases. Beyond the role of lysosomes in substrate degradation, new findings have ascribed to lysosomes the leading role in sensing and responding to cellular nutrients, growth factors and cellular stress. This review aims to integrate recent concepts of basic lysosome biology and pathobiology as a basis for understanding neurodegenerative disease pathogenesis. Here, we discuss the newly recognized signaling functions of lysosomes and specific aspects of lysosome biology in neurons while re-visiting the classical defining criteria for lysosomes and the importance of preserving strict definitions. Our discussion emphasizes dynein-mediated axonal transport of maturing degradative organelles, with further consideration of their roles in synaptic function. We finally examine how distinctive underlying disturbances of lysosomes in various neurodegenerative diseases result in unique patterns of auto/endolysosomal mistrafficking. The rapidly emerging understanding of lysosomal trafficking and disruptions in lysosome signaling is providing valuable clues to new targets for disease-modifying therapies. |
| first_indexed | 2024-12-13T18:51:58Z |
| format | Article |
| id | doaj.art-3d0fad51c4af42dc8ebfa8bdde3b53fc |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-13T18:51:58Z |
| publishDate | 2019-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-3d0fad51c4af42dc8ebfa8bdde3b53fc2022-12-21T23:34:55ZengElsevierNeurobiology of Disease1095-953X2019-02-0112294105Lysosome trafficking and signaling in health and neurodegenerative diseasesPearl P.Y. Lie0Ralph A. Nixon1Center for Dementia Research, Nathan S. Kline Institute, Orangeburg, NY 10962, USA; Department of Psychiatry, New York University Langone Medical Center, New York, NY 10016, USA; Corresponding author at: Center for Dementia Research, Nathan S. Kline Institute, Orangeburg, NY 10962, USA.Center for Dementia Research, Nathan S. Kline Institute, Orangeburg, NY 10962, USA; Department of Psychiatry, New York University Langone Medical Center, New York, NY 10016, USA; Department of Cell Biology, New York University Langone Medical Center, New York, NY 10016, USA; NYU Neuroscience Institute, New York University Langone Medical Center, New York, NY 10016, USALysosomes, single-membrane organelles defined by a uniquely strong acidic lumenal pH and high content of acid hydrolases, are the shared degradative compartments of the endocytic and autophagic pathways. These pathways, and especially lysosomes, are points of particular vulnerability in many neurodegenerative diseases. Beyond the role of lysosomes in substrate degradation, new findings have ascribed to lysosomes the leading role in sensing and responding to cellular nutrients, growth factors and cellular stress. This review aims to integrate recent concepts of basic lysosome biology and pathobiology as a basis for understanding neurodegenerative disease pathogenesis. Here, we discuss the newly recognized signaling functions of lysosomes and specific aspects of lysosome biology in neurons while re-visiting the classical defining criteria for lysosomes and the importance of preserving strict definitions. Our discussion emphasizes dynein-mediated axonal transport of maturing degradative organelles, with further consideration of their roles in synaptic function. We finally examine how distinctive underlying disturbances of lysosomes in various neurodegenerative diseases result in unique patterns of auto/endolysosomal mistrafficking. The rapidly emerging understanding of lysosomal trafficking and disruptions in lysosome signaling is providing valuable clues to new targets for disease-modifying therapies.http://www.sciencedirect.com/science/article/pii/S0969996118301530LysosomeAutophagyLysosomal signalingNutrient-sensingLysosome positioningNeurodegenerative disease |
| spellingShingle | Pearl P.Y. Lie Ralph A. Nixon Lysosome trafficking and signaling in health and neurodegenerative diseases Neurobiology of Disease Lysosome Autophagy Lysosomal signaling Nutrient-sensing Lysosome positioning Neurodegenerative disease |
| title | Lysosome trafficking and signaling in health and neurodegenerative diseases |
| title_full | Lysosome trafficking and signaling in health and neurodegenerative diseases |
| title_fullStr | Lysosome trafficking and signaling in health and neurodegenerative diseases |
| title_full_unstemmed | Lysosome trafficking and signaling in health and neurodegenerative diseases |
| title_short | Lysosome trafficking and signaling in health and neurodegenerative diseases |
| title_sort | lysosome trafficking and signaling in health and neurodegenerative diseases |
| topic | Lysosome Autophagy Lysosomal signaling Nutrient-sensing Lysosome positioning Neurodegenerative disease |
| url | http://www.sciencedirect.com/science/article/pii/S0969996118301530 |
| work_keys_str_mv | AT pearlpylie lysosometraffickingandsignalinginhealthandneurodegenerativediseases AT ralphanixon lysosometraffickingandsignalinginhealthandneurodegenerativediseases |