Reply to Scahill: Behavioral outcome measures in autism.

Comment on: Sulforaphane treatment of autism spectrum disorder (ASD). [Proc Natl Acad Sci U S A. 2014] Uncommon use of common measures in sulforaphane trial. [Proc Natl Acad Sci U S A. 2015

Biosynthesis of Pregnenolone from Cholesterol by Mitochondrial Enzymes of Bovine Adrenal Cortex

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66357/1/j.1432-1033.1978.tb20931.x.pd

Sulforaphane from Broccoli Reduces Symptoms of Autism: A Follow-up Case Series from a Randomized Double-blind Study

Introduction: Autism spectrum disorder (ASD) affects 1 in 68 children, is characterized by impaired social interaction and communication as well as restricted or repetitive behaviors, and varies widely with respect to its causes and presentations. There are no validated pharmacologic treatments for the core symptoms of ASD. The social, medical, and economic burdens of ASD on families and caregivers are profound. We recently showed in a small clinical trial that sulforaphane (SF) from broccoli sprouts could significantly reduce the behavioral symptoms of ASD. Methods: After we completed the intervention phase of the original trial (2011-2013), many caregivers used over-the-counter dietary SF supplements in order to attempt to maintain improvements similar to those noted during the intervention. We periodically followed the progress of study participants through the summer of 2016. Results: Families of 16 of the 26 subjects who received SF as part of the original study responded to requests for further information. Of these subjects, 6 did not continue taking SF supplements after the study. Nine of the 16 subjects are still taking an SF supplement and a 10th planned to. We present the edited testimonials of their caregivers in this case series. Conclusions: Many parents and caregivers articulated the positive effects of SF, both during the intervention phase and in the ensuing 3 years reported herein. These observations may contribute to understanding ASD and to treatments that may alleviate some of its symptoms. Diet- and supplement-based therapies deserve careful consideration for their potential to provide vital clinical as well as biochemical information about ASD

Transcription factors NRF2 and HSF1 have opposing functions in autophagy

Abstract Autophagy plays a critical role in the maintenance of cellular homeostasis by degrading proteins, lipids and organelles. Autophagy is activated in response to stress, but its regulation in the context of other stress response pathways, such as those mediated by heat shock factor 1 (HSF1) and nuclear factor-erythroid 2 p45-related factor 2 (NRF2), is not well understood. We found that the Michael acceptor bis(2-hydoxybenzylidene)acetone (HBB2), a dual activator of NRF2 and HSF1, protects against the development of UV irradiation-mediated cutaneous squamous cell carcinoma in mice. We further show that HBB2 is an inducer of autophagy. In cells, HBB2 increases the levels of the autophagy-cargo protein p62/sequestosome 1, and the lipidated form of microtubule-associated protein light chain 3 isoform B. Activation of autophagy by HBB2 is impaired in NRF2-deficient cells, which have reduced autophagic flux and low basal and induced levels of p62. Conversely, HSF1-deficient cells have increased autophagic flux under both basal as well as HBB2-induced conditions, accompanied by increased p62 levels. Our findings suggest that NRF2 and HSF1 have opposing roles during autophagy, and illustrate the existence of tight mechanistic links between the cellular stress responses