Involvement of lysosomes in the early stages of axon degeneration.
Axon degeneration is a common hallmark of many neurodegenerative diseases, and the underlying mechanism remains largely unknown. Lysosomes are involved in some neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Whether lysosomes are involved in axon degeneration is yet to be elucidated. In this study, we found only about 10% lysosomes remained in axons of cultured superior cervical ganglia (SCGs) after transection for 4h when stained with LysoTracker. Furthermore, we found that lysosomal disruption occurred earlier than morphological changes and loss of mitochondrial membrane potential. In addition, the well-known axon-protective protein Wld(S) delayed injury-induced axon degeneration from both morphological changes and lysosomal disruption. Lysosomal inhibitors including chloroquine and ammonium chloride induced axon degeneration in cultured SCGs, and Wld(S) also slowed down the axon degeneration induced by lysosomal inhibitors. All these data suggest that lysosomal disruption is an early marker of axon degeneration, and inhibition of lysosome induces axon degeneration in a Wld(S)-protectable way. Thus, maintenance of normal lysosomal function might be an important approach to delay axon degeneration in neurodegenerative diseases.
Zheng
Jin
J
Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Yan
Tingting
T
Feng
Yan
Y
Zhai
Qiwei
Q
D000588:Amines; D000643:Ammonium Chloride / Q000633:toxicity; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D002738:Chloroquine / Q000494:pharmacology / Q000633:toxicity; D004396:Coloring Agents; D008247:Lysosomes / Q000378:metabolism / Q000473:pathology*; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017783:Superior Cervical Ganglion / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D014855:Wallerian Degeneration / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*
D000588:Amines; D004396:Coloring Agents; D018696:Neuroprotective Agents; C493330:Red DND-99; D000643:Ammonium Chloride; D002738:Chloroquine