Re: [GRG] normal sense + antisense RNA contribute to dementia

Contact: David Weston
d.weston@ucl.ac.uk
44-203-108-3844
University College London

RNA build-up linked to dementia and motor neuron disease

A new toxic entity associated with genetically inherited forms of
dementia and motor neuron disease has been identified by scientists
at the UCL Institute of Neurology. The toxin is the result of a
genetic mutation that leads to the production of RNA molecules
which could be responsible for the diseases. The findings are
published in the journal Acta Neuropathologica.

Frontotemporal dementia and motor neuron disease are related
neurodegenerative diseases that affect approximately 15,000 people
in the UK. Frontotemporal dementia causes profound personality and
behaviour changes. Motor neuron disease leads to muscle weakness
and eventual paralysis.

The most common known cause for both frontotemporal dementia and
motor neuron disease is an unusual genetic mutation in the C9orf72
gene. The mutation involves a small string of DNA letters at the
beginning of the gene, which expand massively to produce thousands
of copies.

The new research, funded by Alzheimer’s Research UK and the Medical
Research Council, has shown that this DNA expansion acts in a
peculiar way, leading to the generation of unexpected RNA molecules
that could cause the disease.

When a gene is turned on, an RNA copy of the gene’s DNA is
generated. The gene’s DNA code has directionality, so that it is
normally turned on in only one direction, termed the ‘sense
direction’. The new research shows that the DNA expansion is turned
on in both directions.

This leads to the normal sense RNA being produced, as well as RNA
in the opposite direction, termed ‘antisense RNA’. Both RNA types
accumulate into aggregates in the neurons of people with
frontotemporal dementia.

Intriguingly, the research showed that people with more of these
aggregates in their brains developed the disease earlier than
people with less RNA aggregates. This correlation suggests that the
build-up may be important in causing frontotemporal dementia and
motor neuron disease, making the C9orf72 DNA expansion a potential
target for therapy.

Dr Adrian Isaacs, lead researcher at the UCL Institute of
Neurology, said: “”These findings identify new, potentially toxic
molecules in diseases caused by DNA expansions. The next steps will
be to determine how they might kill neurons and how to stop them
building up.”

Dr Simon Ridley, Head of Research at Alzheimer’s Research UK, the
UK’s leading dementia research charity, said: “The discovery of the
C9ORF72 gene was a major step forward for research into
frontotemporal dementia and motor neuron disease, and it’s positive
to see researchers beginning to untangle how this gene may cause
these diseases in some people.

“Alzheimer’s Research UK is delighted to have supported this
promising study. By unravelling some of the biological mechanisms
at play, this research could take us further on the road to new
treatments that are so desperately needed by the thousands of
people with these devastating diseases. For these results to reach
their full potential it’s vital that we continue to invest in
research.”

###

About UCL (University College London)

Founded in 1826, UCL was the first English university established
after Oxford and Cambridge, the first to admit students regardless
of race, class, religion or gender and the first to provide
systematic teaching of law, architecture and medicine.

We are among the world’s top universities, as reflected by our
performance in a range of international rankings and tables.
According to the Thomson Scientific Citation Index, UCL is the
second most highly cited European university and the 15th most
highly cited in the world.

UCL has nearly 25,000 students from 150 countries and more than
9,000 employees, of whom one third are from outside the UK. The
university is based in Bloomsbury in the heart of London, but also
has two international campuses – UCL Australia and UCL Qatar. Our
annual income is more than £800 million.
http://www.ucl.ac.uk | Follow us on Twitter @uclnews | Watch our
YouTube channel YouTube.com/UCLTV

About Alzheimer’s Research UK

Alzheimer’s Research UK is the UK’s leading charity specialising in
finding preventions, treatments and a cure for dementia. To help us
defeat dementia, donate today by visiting
http://www.alzheimersresearchuk.org or calling 0300 111 5555. We
are currently supporting dementia research projects worth over £20
million in leading Universities across the UK.

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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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