Nox1 Downregulators: A New Class of Therapeutics.


FULLTEXT
Published:
09.14.2019
|
Last Revised:
09.17.2019
PMID:
31518594
Steroids
Journal Article

Molecular Internal Medicine, University of Zürich, Zürich, Switzerland; Andreas Grüntzig Foundation, Zürich, Switzerland. Electronic address: barton@access.uzh.ch.
Division of Cardiology, Triemli City Hospital, Zürich, Switzerland; Institute of Primary Care, University of Zürich, Zürich, Switzerland.
Division of Molecular Medicine, Department of Internal Medicine, Albuquerque, NM, U.S.A; University of New Mexico Comprehensive Cancer Center, University of New Mexico Health Sciences Center, Albuquerque, NM, U.S.A.

Abstract

Chronic non-communicable diseases share the pathomechanism of increased reactive oxygen species (ROS) production by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases, known as Nox. The recent discovery that expression of Nox1, a Nox isoform that has been implicated in the pathogenesis of cardiovascular and kidney disease, is regulated by the expression and activity of G protein-coupled estrogen receptor (GPER) led to the identification of orally active small-molecule GPER blockers as selective Nox1 downregulators (NDRs). Preclinical studies using NDRs have demonstrated beneficial effects in vascular disease, hypertension, and glomerular renal injury. These findings suggest the therapeutic potential of NDRs, which reduce Nox1 protein levels, not only for cardiovascular disease conditions including arterial hypertension, pulmonary hypertension, heart failure with preserved ejection fraction (HFpEF), and chronic renal disease, but also for other non-communicable diseases, such as cerebrovascular disease and vascular dementia, Alzheimer's disease, autoimmune diseases and cancer, in which elevated Nox1-derived ROS production plays a causal role.

GrantID: P20 GM121176, Acronym: GM, Agency: NIGMS NIH HHS, Country: United States | GrantID: P30 CA118100, Acronym: CA, Agency: NCI NIH HHS, Country: United States | GrantID: R01 CA163890, Acronym: CA, Agency: NCI NIH HHS, Country: United States | GrantID: R01 CA194496, Acronym: CA, Agency: NCI NIH HHS, Country: United States