[GRG] a switch to generate and aid survival of neurons identified


Contact: Susan Gammon
Sanford-Burnham Medical Research Institute

A ‘switch’ in Alzheimer’s and stroke patient brains that prevents
the generation and survival of neurons

La Jolla, Calif., July 3, 2014 – A new study by researchers at
Sanford-Burnham Medical Research Institute (Sanford-Burnham) has
identified a chemical “switch” that controls both the generation of
new neurons from neural stem cells and the survival of existing
nerve cells in the brain. The switch that shuts off the signals
that promote neuron production and survival is in abundance in the
brains of Alzheimer’s patients and stroke victims. The study,
published July 3 in Cell Reports, suggests that chemical switch,
MEF2, may be a potential therapeutic target to protect against
neuronal loss in a variety of neurodegenerative diseases, such as
Alzheimer’s, Parkinson’s and autism.

“We have shown that when nitric oxide (NO)—a highly reactive free
radical—reacts with MEF2, MEF2 can no longer bind to and activate
the genes that drive neurogenesis and neuronal survival,” said
Stuart Lipton, M.D., Ph.D., director and professor in the
Neuroscience and Aging Research Center at Sanford-Burnham, and a
practicing clinical neurologist. “What’s unique here is that a
single alteration to MEF2 controls two distinct events—the
generation of new neurons and the survival of existing neurons,”
added Lipton, who is senior author of the study.

In the brain, transcription factors are critical for linking
external stimuli to protein production, enabling neurons to adapt
to changing environments. Members of the MEF2 family of
transcription factors have been shown to play an important role in
neurogenesis and neuronal survival, as well as in the processes of
learning and memory. And, mutations of the MEF2 gene have been
associated with a range of neurodegenerative disorders, including
Alzheimer’s and autism.

The process of NO-protein modifications—known as S-
nitrosylation—was first described by Lipton and collaborators some
20 years ago. S-nitrosylation has important regulatory functions
under normal physiological conditions throughout the body. However,
with aging, environmental toxins, or stress-related injuries,
abnormal S-nitrosylation reactions can occur, contributing to
disease pathogenesis.

“Our laboratory had previously shown that S-nitrosylation of MEF2
controlled neuronal survival in Parkinson’s disease,” said Lipton.
“Now we have shown that this same reaction is more ubiquitous,
occurring in other neurological conditions such as stroke and
Alzheimer’s disease. While the major gene targets of MEF2 may be
different in various diseases and brain areas, the remarkable new
finding here is that we may be able to treat each of these
neurological disorders by preventing a common S-nitrosylation
modification to MEF2.

“The findings suggest that the development of a small therapeutic
molecule—one that can cross the blood-brain barrier and block S-
nitrosylation of MEF2 or in some other way increase MEF2
transcriptional activity—could promote new brain cell growth and
protect existing cells in several neurodegenerative disorders,”
added Lipton.

“We have already found several such molecules in our high-
throughput screening and drug discovery efforts, so the potential
for developing new drugs to attack this pathway is very exciting,”
said Lipton.


About Johnny Adams

My full-time commitment is to slow and ultimately reverse age related functional decline to increase healthy years of life. I’ve been active in this area since the 1970s, steadily building skills and accomplishments. I have a good basic understanding of the science of aging, and have many skills that complement those of scientists so they can focus on science to advance our shared mission. Broad experience Top skills: administration, management, information technology (data and programming), communications, writing, marketing, market research and analysis, public speaking, forging ethical win-win outcomes among stakeholders (i.e. high level "selling"). Knowledge in grant writing, fundraising, finance. Like most skilled professionals, I’m best described as a guy who defines an end point, then figures out how to get there. I enjoy the conception, design, execution and successful completion of a grand plan. Executive Director Gerontology Research Group (GRG). Manages Email discussion forum, web site, meetings and oversees supercentenarian (oldest humans, 110+ years) research. CEO / Executive Director Carl I. Bourhenne Medical Research Foundation (Aging Intervention Foundation), an IRS approved 501(c)(3) nonprofit. http://www.AgingIntervention.org Early contributor to Supercentenarian Research Foundation. Co-Founder Geroscience Healthspan Forum. Active contributor to numerous initiatives to increase healthy years of life. Co-authored book on conventional, practical methods available today to slow the processes of aging – nutrition, exercise, behavior modification and motivation, stress reduction, proper supplementation, damage caused by improper programs, risk reduction and others. Fundamental understanding of, and experience in the genomics of longevity (internship analyzing and curating longevity gene papers). Biological and technical includes information technology, software development and computer programming, bioinformatics and protein informatics, online education, training programs, regulatory, clinical trials software, medical devices (CAT scanners and related), hospital electrical equipment testing program. Interpersonal skills – good communication, honest, well liked, works well in teams or alone. Real world experience collaborating in interdisciplinary teams in fast paced organizations. Uses technology to advance our shared mission. Education: MBA 1985 University of Southern California -- Deans List, Albert Quon Community Service Award (for volunteering with the American Longevity Association and helping an elderly lady every other week), George S. May Scholarship, CA State Fellowship. BA psychology, psychobiology emphasis 1983 California State University Fullerton Physiological courses as well as core courses (developmental, abnormal etc). UCLA Psychobiology 1978, one brief but fast moving and fulfilling quarter. Main interest was the electrochemical basis of consciousness. Also seminars at the NeuroPsychiatric Institute. Other: Ongoing conferences, meetings and continuing education. Aging, computer software and information technology. Some molecular biology, biotech, bio and protein informatics, computer aided drug design, clinical medical devices, electronics, HIPAA, fundraising through the Assoc. of Fundraising Professionals. Previous careers include: Marketing Increasing skill set and successes in virtually all phases, with valuable experience in locating people and companies with the greatest need and interest in a product or service, and sitting across the table with decision makers and working out agreements favorable to all. Information Technology: Management, data analysis and programming in commercial and clinical trials systems, and bioinformatics and protein informatics. As IT Director at Newport Beach, CA based technology organization Success Family of Continuing Education Companies, provided online software solutions for insurance and financial professionals in small to Fortune 500 size companies. We were successful with lean team organization (the slower moving competition was unable to create similar software systems). Medical devices: At Omnimedical in Paramount CA developed and managed quality assurance dept. and training depts. for engineers, physicians and technicians. Designed hospital equipment testing program for hospital services division. In my early 20’s I was a musician, and studied psychology and music. Interned with the intention of becoming a music therapist. These experiences helped develop valuable skills used today to advance our shared mission of creating aging solutions.
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