[GRG] new proteins for removing misfolded proteins discovered

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A new cellular garbage control pathway with relevance for human
neurodegenerative diseases

July 18, 2014

Several human neurodegenerative diseases, including Alzheimer’s,
Parkinson’s and Huntington’s disease but also ageing, are linked to
an accumulation of abnormal and aggregated proteins in cells.
Cellular “garbage” of this type can be removed from cells by
sweeping them to a cellular recycling station known as the
lysosome. Scientists at the Max Planck Institute of Biochemistry in
Martinsried, Germany, now discovered a new family of helper
proteins that recognize labeled cellular protein waste and guide
them efficiently to the lysosome for destruction and subsequent
recycling into their reusable compounds. The results of this study,
now published in the journal Cell, are crucial for our
understanding how cells remove cellular waste and will open new
avenues for studies aimed to fight neurodegenerative diseases.

The newly identified proteins, termed CUET proteins (for
Cue5/Tollip adaptors; shown in red), recognize pathological protein
aggregates (cellular waste), including those of human
neurodegenerative diseases. CUET proteins also associate with
specific cellular structures that target the whole complex to the
cellular waste disposal and recycling station, the lysosome.
Zoom Image

The newly identified proteins, termed CUET proteins (for
Cue5/Tollip… [more]

Stefan Jentsch © MPI of Biochemistry

Proteins, the components of our body that execute, control and
organize basically all functions in our cells, are made out of
strings of amino acids, which – like an origami – are folded into
specific and complex three-dimensional structures according to
their desired functions. However, since folding and maintaining of
such structures is highly sensitive to cellular or environmental
stress, proteins can potentially misfold or form clumps
(aggregates). Such undesired protein waste can be toxic for cells
and may even lead to cell death. Because several human
neurodegenerative diseases are known to be linked to an
accumulation of abnormal protein aggregates, basic science aimed to
understand how cells remove cellular garbage is elementary for
designing strategies for a potential prevention or cure of such
disorders.

Scientists in the laboratory of Stefan Jentsch at the MPIB now
successfully used baker’s yeast for screening for new cellular
waste disposal pathways. Kefeng Lu, a postdoctoral researcher from
China, discovered a new class of helper proteins (termed CUET
proteins) present both in yeast and humans that recognize cellular
garbage earmarked for disposal by an attached label in the form of
the ubiquitously existing protein known as “ubiquitin”.
Importantly, these newly identified helper proteins channel the
cellular garbage by a “self-eating” pathway (autophagy) to the
lysosome, a compartment of cells dedicated for destruction and
recycling. The Max Planck scientists could also show that a toxic
protein related to the abnormal, aggregate-forming protein
“huntingtin” of patients with the neurodegenerative Huntington’s
disease is efficiently destroyed by the newly identified pathway.
Remarkably, this pathway seems specific for aggregated proteins
like huntingtin and appears to be more potent than previously
discovered cellular garbage disposal mechanisms.

Because the identified cellular disposal mechanism operates in
yeast as well, the researches will now take full advantage of its
powerful experimental possibilities to investigate this pathway
further. A detailed analysis of this mechanism will be crucial to
understand how aggregate-forming proteins lead to human diseases
and may help to develop concepts for possible disease preventions.

Original Publication:
K. Lu, I. Psakhye and S. Jentsch: Autophagic clearance of polyQ
proteins mediated by the conserved CUET protein family. Cell, July
17, 2014.
DOI: 10.1016/j.cell.2014.05.048

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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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