Identification of novel neuroprotectants against vincristine-induced neurotoxicity in iPSC-derived neurons.

Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling side effect of cancer chemotherapy that can often limit treatment options for cancer patients or have life-long neurodegenerative consequences that reduce the patient's quality of life. CIPN is caused by the detrimental actions of various chemotherapeutic agents on peripheral axons. Currently, there are no approved preventative measures or treatment options for CIPN, highlighting the need for the discovery of novel therapeutics and improving our understanding of disease mechanisms.

Identification of novel neuroprotectants against vincristine-induced neurotoxicity in iPSC-derived neurons.

Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling side effect of cancer chemotherapy that can often limit treatment options for cancer patients or have life-long neurodegenerative consequences that reduce the patient's quality of life. CIPN is caused by the detrimental actions of various chemotherapeutic agents on peripheral axons. Currently, there are no approved preventative measures or treatment options for CIPN, highlighting the need for the discovery of novel therapeutics and improving our understanding of disease mechanisms.

Bortezomib-induced neurotoxicity in human neurons is the consequence of nicotinamide adenine dinucleotide depletion.

The proteosome inhibitor bortezomib has revolutionized the treatment of multiple hematologic malignancies, but in many cases, its efficacy is limited by a dose-dependent peripheral neuropathy. We show that human induced pluripotent stem cell (hiPSC)-derived motor neurons and sensory neurons provide a model system for the study of bortezomib-induced peripheral neuropathy, with promising implications for furthering the mechanistic understanding of and developing treatments for preventing axonal damage. Human neurons in tissue culture displayed distal-to-proximal neurite degeneration when exposed to bortezomib.

High-throughput functional comparison of promoter and enhancer activities.

Promoters initiate RNA synthesis, and enhancers stimulate promoter activity. Whether promoter and enhancer activities are encoded distinctly in DNA sequences is unknown. We measured the enhancer and promoter activities of thousands of DNA fragments transduced into mouse neurons.