2016
DOI: 10.18632/aging.101144
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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… Show more

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Cited by 42 publications
(40 citation statements)
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References 59 publications
(72 reference statements)
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“…However, the exact mechanism underlying mitochondrial dysfunction-induced lysosome impairment is incompletely understood. Recent studies found a critical role of TFEB in many processes in respect to enhanced autophagy and lysosomal function [33,34]. Notably, under conditions of lysosomal stress, TFEB is translocated to the nucleus in several models of lysosomal storage disorders, initiating the expansion of the lysosomal compartment of the cell and the degradation of accumulated lysosomal contents [35].…”
Section: Figure 11 Schematic Representation Of the Regulatory Role Omentioning
confidence: 99%
“…However, the exact mechanism underlying mitochondrial dysfunction-induced lysosome impairment is incompletely understood. Recent studies found a critical role of TFEB in many processes in respect to enhanced autophagy and lysosomal function [33,34]. Notably, under conditions of lysosomal stress, TFEB is translocated to the nucleus in several models of lysosomal storage disorders, initiating the expansion of the lysosomal compartment of the cell and the degradation of accumulated lysosomal contents [35].…”
Section: Figure 11 Schematic Representation Of the Regulatory Role Omentioning
confidence: 99%
“…Both Aβ precursor protein and tau are expressed by breast cancer cells [42], [43], and preclinical studies suggest that administration of peripheral tau or Aβ seeds results in tau or amyloid-related CNS pathologies, respectively [44], [45]. We previously demonstrated that breast cancer chemotherapy impairs autophagy [46], which may exacerbate normal age-related weakening of clearance mechanisms, worsening accumulation of toxins such as Aβ and tau. However, the effect of tau and Aβ expression from breast cancer cells on the CNS is currently unknown.…”
Section: Discussionmentioning
confidence: 99%
“…The supernatant sample was used for estimating antioxidant enzymes markers. The total protein content was measured by the technique designed by Taylor et al The catalase (CAT) action was evaluated by Liu et al method . The superoxide dismutase (SOD) action was assessed by Mayer et al method .…”
Section: Methodsmentioning
confidence: 99%