Abstract
The therapeutic benefits of adrenocorticotropic hormone in multiple sclerosis are usually ascribed to its corticotropic actions.
Introduction
Adrenocorticotropic hormone (ACTH) is cleaved from its pro-opiomelanocortin (POMC) prohormone as are α-melanocyte-stimulating hormone (α-MSH), β-MSH and γ-MSH ( Figure 1a ). 1 ACTH and α-, β- and γ-MSH comprise the melanocortins. There are five melanocortin receptors (MCRs).
MCR distributions and functions
MC1R was the first melanocortin receptor cloned; 8 cloning of four additional MCRs followed promptly. MCRs are found in multiple cell types, but even today knowledge of the extent of their expression remains incomplete. MC1R is expressed in skin in melanocytes and in monocytes, neutrophils and lymphocytes.
Ligands for MCRs
All melanocortins share the histidine, phenylalanine, arginine, tryptophan (HFRW) core sequence. 1 Shared HFRW explains why all melanocortins bind to every MCR except MC2R.
Direct immunomodulatory effects of melanocortins
α-MSH restrains the nuclear factor-kappaB (NF-κB) transcription factor. 9, 13, 14 NF-κB remains inactive in resting cells, bound in the cytoplasm to IκB inhibitory protein family members. Phosphorylation of IκB by cytokines, bacterial products, or viruses causes IκB degradation.
CNS-mediated anti-inflammatory effects
Animal studies using intracerebroventricular melanocortins 1 point to multiple CNS POMC + neuron-initiated and CNS-confined effects. Because systemic ACTH induces such effects, the agent must somehow activate CNS-restricted POMC + neurons. 7
Melanocortin signaling and drug safety
Drug safety is a constant concern. Complications may surface long after a drug is approved. ACTH, used for 60 years to treat thousands of patients, has an established safety profile. Because ACTH has been linked to corticotropic effects, many assume that side effects of ACTH reflect those associated with corticosteroids.
What did Bennet say about Pruitt's decision to repeal the Clean Power Plan?
In October 2017, Bennet was one of 19 senators to sign a letter to Administrator of the Environmental Protection Agency Scott Pruitt questioning Pruitt's decision to repeal the Clean Power Plan, asserting that Pruitt used "mathematical sleights of hand to overstate the costs of industry compliance with the 2015 Rule and understate the benefits that will be lost if the 2017 repeal is finalized", and that science denial and math tricks fail to "satisfy the requirements of the law, nor will it slow the increase in frequency and intensity of extreme weather events, the inexorable rise in sea levels, or the other dire effects of global warming that our planet is already experiencing."
Who is Bennet in Colorado?
Michael Farrand Bennet (born November 28, 1964) is an American businessman, lawyer, and politician who has served as the senior United States Senator from Colorado since 2009. A member of the Democratic Party, he was appointed to the seat when Senator Ken Salazar became Secretary of the Interior.
What did Bennet do in 2009?
In September 2009, Bennet cosponsored the DREAM Act (S. 729), which proposed amending the Illegal Immigration Reform and Immigrant Responsibility Act of 1996 by giving residency to immigrants enrolled in higher education programs or serving in the military. In 2013, he was a member of the Gang of Eight, a bipartisan group of four Democratic and four Republican U.S. Senators who introduced comprehensive immigration reform legislation. Their bill, the Border Security, Economic Opportunity, and Immigration Modernization Act of 2013, passed the U.S. Senate with a vote of 68-32, but stalled in the House due to opposition from the Republican majority. He later cosponsored the Dream Act of 2017. After President Trump ended the Deferred Action for Childhood Arrivals ( DACA) program, Bennet worked with a bipartisan group of Senators to provide a pathway to citizenship for Dreamers with stronger border protections.
Why did Bennet get a C+?
Gun law. As of 2010, Bennet had earned a "C+" grade from the National Rifle Association for a mixed record regarding his votes for gun rights. In 2012, Bennet joined then Colorado Senator Mark Udall in asking for stricter gun control, in response to the Sandy Hook Elementary School shooting.
Is Bennet a cosponsor of the EPA Superfund?
In March 2019, Bennet was an original cosponsor of a bipartisan bill intended to mandate that the Environmental Protection Agency declare per- and polyfluoroalkyl substances as hazardous substances that can be addressed with cleanup funds via the EPA Superfund law and require that polluters undertake or pay for remediation within a year of the bill's enaction.
Who is Senator Bennet?
Michael Farrand Bennet (born November 28, 1964) is an American businessman, lawyer, and politician who has served as the senior United States Senator from Colorado since 2009.
Did Bennet participate in the Chris Murphy gun control filibuster?
Bennet participated in the Chris Murphy gun control filibuster, demanding that gun laws be changed in the wake of the Orlando nightclub shooting. During his participation in the filibuster, Bennet talked about the 2012 Aurora, Colorado shooting, citing that as a response to the shooting, the state of Colorado closed gun sale loopholes and now requires background checks for any gun purchase.
Overview
Michael Farrand Bennet (born November 28, 1964) is an American attorney, businessman, and politician serving as the senior United States senator from Colorado, a seat he has held since 2009. A member of the Democratic Party, he was appointed to the seat when Senator Ken Salazar became Secretary of the Interior. Bennet previously worked as a managing director for the Anschutz Inv…
Early life and education
Bennet was born in New Delhi, India. His mother is Susanne Christine Bennet (née Klejman), a retired elementary school librarian and Jewish Holocaust survivor who was born in 1938 in Warsaw, Poland, and immigrated to the United States with her family in 1950. Her parents survived imprisonment in the Warsaw Ghetto. His father is Douglas J. Bennet, who was born in New Jersey, a Christian who served as an aide to Chester Bowles, then the U.S. ambassador to India. Douglas …
Early career
From 1988 until 1990, when he left to attend Yale, he served as an aide to Ohio governor Richard Celeste. After law school he served as a law clerk for the 4th Circuit Court of Appeals and as an associate to Washington, D.C. attorney Lloyd Cutler. He then served as Counsel to the Deputy Attorney General during the Bill Clinton administration. His father, Douglas Bennet worked in the Clinton White House as well, as Assistant Secretary of State for International Organization Affairs. …
U.S. Senate
On January 3, 2009, Bennet was named by Colorado governor Bill Ritter to fill the seat in the United States Senate vacated by United States Secretary of the Interior Ken Salazar on January 20. Ritter chose Bennet after interviewing several prominent Colorado Democrats, and Bennet took the job with the blessing of Hickenlooper. Upon taking office on January 21, 2009, he became the younges…
Political positions
Most of Bennet's positions are considered liberal. The American Conservative Union gave Bennet a 6% lifetime conservative rating in 2020.
Bennet supports abortion rights and has voted to continue federal funding to Planned Parenthood. After Roe v. Wade was overturned in June 2022, Bennet said that the "radical majority on the Supreme Court demolished fifty years of …
2020 presidential campaign
Bennet's 2020 presidential campaign began on May 2, 2019, when he officially declared his candidacy during an appearance on CBS This Morning. Bennet was previously mentioned as a possible presidential candidate following his viral response to Senator Ted Cruz in January 2019. In February and March 2019 he traveled to early primary states such as Iowa and New Hampshire. In late Marc…
Personal life
On October 26, 1997, Bennet married Earthjustice Legal Defense Fund attorney Susan Diane Daggett, in Marianna, Arkansas. They have three daughters and reside in Denver's Congress Park neighborhood.
Though not raised in an observant household, Bennet acknowledges his Jewish roots. He has said that he was "raised with two different heritages, one [that] w…
See also
• List of United States senators born outside the United States