Jose Felix Moruno-Manchon, Ndidi-Ese Uzor, Shelli R. Kesler, Jeffrey S. Wefel, Debra M. Townley, Archana Sidalaghatta Nagaraja, Sunila Pradeep, Lingegowda S. Mangala, Anil K. Sood, Andrey S. Tsvetkov
Abstract:Doxorubicin, a commonly used chemotherapy agent, induces severe cardio- and neurotoxicity. Molecular mechanisms of cardiotoxicity have been extensively studied, but mechanisms by which doxorubicin exhibits its neurotoxic properties remain unclear. Here, we show that doxorubicin impairs neuronal autophagy, leading to the accumulation of an autophagy substrate p62. Neurons treated with doxorubicin contained autophagosomes, damaged mitochondria, and lipid droplets. The brains from mice treated with pegylated lipo…
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