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Full-Text Articles in Medicine and Health Sciences
Aldo-Keto Reductases And Cancer Drug Resistance, Trevor M. Penning, Sravan Jonnalagadda, Paul C. Trippier, Tea Lanišnik Rižner
Aldo-Keto Reductases And Cancer Drug Resistance, Trevor M. Penning, Sravan Jonnalagadda, Paul C. Trippier, Tea Lanišnik Rižner
Journal Articles: Pharmaceutical Sciences
Human aldo-keto reductases (AKRs) catalyze the NADPH-dependent reduction of carbonyl groups to alcohols for conjugation reactions to proceed. They are implicated in resistance to cancer chemotherapeutic agents either because they are directly involved in their metabolism or help eradicate the cellular stress created by these agents (e.g., reactive oxygen species and lipid peroxides). Furthermore, this cellular stress activates the Nuclear factor-erythroid 2 p45-related factor 2 (NRF2)-Kelch-like ECH-associated protein 1 pathway. As many human AKR genes are upregulated by the NRF2 transcription factor, this leads to a feed-forward mechanism to enhance drug resistance. Resistance to major classes of chemotherapeutic agents (anthracyclines, …
Patient-Derived Induced Pluripotent Stem Cell Models For Phenotypic Screening In The Neuronal Ceroid Lipofuscinoses, Ahmed Morsy, Angelica V. Carmona, Paul C. Trippier
Patient-Derived Induced Pluripotent Stem Cell Models For Phenotypic Screening In The Neuronal Ceroid Lipofuscinoses, Ahmed Morsy, Angelica V. Carmona, Paul C. Trippier
Journal Articles: Pharmaceutical Sciences
Batten disease or neuronal ceroid lipofuscinosis (NCL) is a group of rare, fatal, inherited neurodegenerative lysosomal storage disorders. Numerous genes (CLN1-CLN8, CLN10-CLN14) were identified in which mutations can lead to NCL; however, the underlying pathophysiology remains elusive. Despite this, the NCLs share some of the same features and symptoms but vary in respect to severity and onset of symptoms by age. Some common symptoms include the progressive loss of vision, mental and motor deterioration, epileptic seizures, premature death, and in the rare adult-onset, dementia. Currently, all forms of NCL are fatal, and no curative treatments are available. Induced pluripotent stem …