When the same treatment has different response: The role of pharmacogenomics in statin therapy

Zheng, Edward; Madura, Paulina; Grandos, Jakub; Broncel, Marlena; Pawlos, Agnieszka; Woźniak, Ewelina; Gorzelak-Pabiś, Paulina

doi:10.1016/j.biopha.2023.115966

Cited by 3 publications

(1 citation statement)

References 141 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also, very recently it has been proposed that different biological processes may underlie the formation of specific types of cholesterol-rich deposits associated with AMD (e.g., drusen vs. sub-drusenoid deposits (SDDs)), resulting in different disease states); hence, different therapeutic intervention strategies may be required to resolve those distinct pathologies [ 94 ]. More effective therapeutic interventions in such diseases may require a combination of pharmacological, dietary, and gene therapy-based interventions, guided in part by data-mining approaches [ 95 ] and application of refined pharmacogenomics [ 96 ] as well as use of more recently developed and emerging pharmaceuticals for improved lipid management [ 97 ].…”

Section: Discussionmentioning

confidence: 99%

Bottlenecks in the Investigation of Retinal Sterol Homeostasis

Ramachandra Rao,

Fliesler

2024

Biomolecules

View full text Add to dashboard Cite

Sterol homeostasis in mammalian cells and tissues involves balancing three fundamental processes: de novo sterol biosynthesis; sterol import (e.g., from blood-borne lipoproteins); and sterol export. In complex tissues, composed of multiple different cell types (such as the retina), import and export also may involve intratissue, intercellular sterol exchange. Disruption of any of these processes can result in pathologies that impact the normal structure and function of the retina. Here, we provide a brief overview of what is known currently about sterol homeostasis in the vertebrate retina and offer a proposed path for future experimental work to further our understanding of these processes, with relevance to the development of novel therapeutic interventions for human diseases involving defective sterol homeostasis.

show abstract

Section: Discussionmentioning

confidence: 99%

Bottlenecks in the Investigation of Retinal Sterol Homeostasis

Ramachandra Rao,

Fliesler

2024

Biomolecules

View full text Add to dashboard Cite

show abstract

Off‐target effects of statins: molecular mechanisms, side effects and the emerging role of kinases

Lagunas‐Rangel,

Liepinsh,

Fredriksson

et al. 2024

British J Pharmacology

View full text Add to dashboard Cite

Statins are one of the most important classes of drugs. In this analytical review, we elucidate the intricate molecular mechanisms and toxicological rationale regarding both the on‐ (targeting 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase [HMGCR]) and off‐target effects of statins. Statins interact with a number of membrane kinases, such as epidermal growth factor receptor (EGFR), erb‐b2 receptor tyrosine kinase 2 (HER2) and MET proto‐oncogene, receptor tyrosine kinase (MET), as well as cytosolic kinases, such as SRC proto‐oncogene, non‐receptor tyrosine kinase (Src) and show inhibitory activity at nanomolar concentrations. In addition, they interact with calcium ATPases and peroxisome proliferator‐activated receptor α (PPARα/NR1C1) at higher concentrations. Statins interact with mitochondrial complexes III and IV, and their inhibition of coenzyme Q10 synthesis also impairs the functioning of complexes I and II. Statins act as inhibitors of kinases, calcium ATPases and mitochondrial complexes, while activating PPARα. These off‐target effects likely contribute to the side effects observed in patients undergoing statin therapy, including musculoskeletal symptoms and hepatic effects. Interestingly, some off‐target effects of statins could also be the cause of favourable outcomes, relating to repurposing statins in conditions such as inflammatory disorders and cancer.

show abstract