Y-27632, an inhibitor of the Rho-associated kinase ROCK, is a therapeutic lead for Huntington disease (HD). The downstream targets that mediate its inhibitory effects on huntingtin (Htt) aggregation and toxicity are unknown. We have identified profilin, a small actin-binding factor that also interacts with Htt, as being a direct target of the ROCK1 isoform. The overexpression of profilin reduces the aggregation of polyglutamine-expanded Htt and androgen receptor (AR) peptides. This requires profilin's G-actin binding activity and its direct interaction with Htt, which are both inhibited by the ROCK1-mediated phosphorylation of profilin at Ser-137. Y-27632 blocks the phosphorylation of profilin in HEK293 cells and primary neurons, which maintains profilin in an active state. The knockdown of profilin blocks the inhibitory effect of Y-27632 on both AR and Htt aggregation. A signaling pathway from ROCK1 to profilin thus controls polyglutamine protein aggregation and is targeted by a promising therapeutic lead for HD.
- American Society for Microbiology
- Phosphorylation of profilin by rock1 regulates polyglutamine ...
Overview of Using Lead Through the History
Various sources assumed the share of guilt in the fall of the Roman Empire due to the use of the lead pipe, Devonshire colic in the 18th century, poisoning from the addition of lead acetate to wine and pediatric lead poisoning. Not only production but also the use of pottery for centuries caused poisoning among the population. When a piece of pottery covered with lead glaze is not heated enough, which happens in many developing countries, acidic products and liquids, such as salad dressings, citrus juice, and...
Are Universal Wastes DOT Regulated?
The answer is yes, no, and maybe. Under the DOT regulations, hazardous wastes are regulated in all modes (ground, air, rail, vessel) of transportation. EPA has classified specific hazardous waste as Universal Waste to streamline the process and encourage recycling of these materials (see 40 CFR 273). EPA has specifically addressed the DOT requirements for these waste at 40 CFR 273.52 as follows: § 273.52 – Waste management.(a) A universal waste transporter must comply with all applicable U.S....
If lead ammunition is bad for people and the environment, why do we still use it?
Concerns about regulation, skepticism about the science and misperceptions about costs are slowing the transition to nontoxic alternatives. Andrea Goodnight knows firsthand what lead poisoning looks like. A veterinarian at the Oakland Zoo, Goodnight treats endangered California condors when testing shows dangerous levels of the toxic metal in their blood. If blood lead levels get too high, condors, eagles and other raptors “regurgitate everything and can’t hold anything down, so basically they’r...
Top International News in Chemical Policy and Regulation
AUSTRALIA Australia Releases Third Consultation Paper Concerning NICNAS Reform:On April 29, 2016, the National Industrial Chemicals Notification and Assessment Scheme (NICNAS) published thethird consultation paperon itsreform initiative. This consultation paper summarizes the main stakeholder comments on thesecond consultation paper, and builds on the themes in the second consultation paper to describe key changes to the reform proposals. The third consultation paper provides further details and addresses...
Together we can get the lead out
If there is one lesson to be learned from the Flint crisis, it is this: Our communities will be safer in the long run with no lead pipes in the ground. That’s why the board of the American Water Works Association – recognizing our first core principle is the protection of public health -- voted unanimously on March 7 to forge on a path toward the removal of all lead service lines. AWWA believes that as water professionals and a broader society, we should seize this moment of increased awareness to...