Medicine and Health Sciences Commons^™

Age-Related Decline In Hippocampal Tyrosine Phosphatase Ptpro Is A Mechanistic Factor In Chemotherapy-Related Cognitive Impairment., Zhimeng Yao, Hongmei Dong, Jianlin Zhu, Liang Du, Yichen Luo, Qing Liu, Shixin Liu, Yusheng Lin, Lu Wang, Shuhong Wang, Wei Wei, Keke Zhang, Qingjun Huang, Xiaojun Yu, Weijiang Zhao, Haiyun Xu, Xiaofu Qiu, Yunlong Pan, Xingxu Huang, Sai-Ching Jim Yeung, Dianzheng Zhang, Hao Zhang

PCOM Scholarly Papers

Chemotherapy-related cognitive impairment (CRCI) or "chemo brain" is a devastating neurotoxic sequela of cancer-related treatments, especially for the elderly individuals. Here we show that PTPRO, a tyrosine phosphatase, is highly enriched in the hippocampus, and its level is tightly associated with neurocognitive function but declined significantly during aging. To understand the protective role of PTPRO in CRCI, a mouse model was generated by treating Ptpro-/- female mice with doxorubicin (DOX) because Ptpro-/- female mice are more vulnerable to DOX, showing cognitive impairments and neurodegeneration. By analyzing PTPRO substrates that are neurocognition-associated tyrosine kinases, we found that SRC and EPHA4 are …