High-throughput screening identifies a novel small-molecule modulator of Hsp70 that selectively enhances ubiquitination and degradation of misfolded neuronal NO synthase.

The Hsp90 and Hsp70 chaperones act as a protein quality control system for several hundred client proteins, including many implicated in neurodegenerative disorders. Hsp90 and Hsp70 are widely thought to be important drug targets. Although many structurally distinct compounds have been developed to target Hsp90, relatively few are known to target Hsp70 and even fewer have been tested in protein quality control systems.

Therapeutic targeting of the polyglutamine androgen receptor in Spinal and Bulbar Muscular Atrophy.

Introduction: Spinal and Bulbar Muscular Atrophy (SBMA) is a slowly progressive, X-linked, and sex-limited degenerative disorder affecting lower motor neurons and skeletal muscle which lacks disease-modifying therapies. This disease is caused by a CAG/polyglutamine (polyQ) tract expansion in the androgen receptor (AR) gene, and its pathogenesis is driven by toxic gain-of-function mechanisms. Affected men develop proximal limb and bulbar muscle weakness along with signs of partial androgen insensitivity.

A qualitative study of perceptions of the care pathway for familial hypercholesterolemia: screening, diagnosis, treatment, and family cascade screening.

Background: Familial hypercholesterolemia (FH) is an autosomal dominant genetic condition that carries increased risk for premature atherosclerotic cardiovascular disease, cardiovascular events, and death. Due to low uptake of evidence-based practices, up to 80% of FH patients remain undiagnosed and most are undertreated. This project aimed to understand patient and clinician perceptions across the care pathway of evidence-based diagnosis and treatment of FH, to inform implementation strategy design for two clinical trials seeking to increase evidence-based care.

California Stress, Trauma, and Resilience Study (CalSTARS) protocol: A multiomics-based cross-sectional investigation and randomized controlled trial to elucidate the biology of ACEs and test a precision intervention for reducing stress and enhancing resilience.

Adverse Childhood Experiences (ACEs) are very common and presently implicated in 9 out of 10 leading causes of death in the United States. Despite this fact, our mechanistic understanding of how ACEs impact health is limited. Moreover, interventions for reducing stress presently use a one-size-fits-all approach that involves no treatment tailoring or precision.