Multiple System Atrophy is Described as First New Human Prion Disease Identified in 50 Years

By Nicholas Weiler (UCSF News Center) on August 31, 2015

Multiple System Atrophy (MSA), a neurodegenerative disorder with similarities to Parkinson’s disease, is caused by a newly discovered type of prion, akin to the misfolded proteins involved in incurable progressive brain diseases such Creutzfeldt-Jakob disease (CJD), according to two new research papers led by scientists at UC San Francisco.

The findings suggest new approaches to developing treatments for MSA, which currently has no cure, but also raise a potential concern for clinicians or scientists who come in contact with MSA tissue.

The new findings mark the first discovery of a human disease caused by a new prion in 50 years, since work at the National Institutes of Health in the 1960s showed that human brain tissue infected with CJD could transmit neurodegeneration to chimpanzees.

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Three IND faculty—Keiser, Kampmann, Kokel—honored as distinguished investigators from the Allen Family Foundation



The Paul G. Allen Family Foundation recently named IND faculty members Michael Keiser, Martin Kampmann, and David Kokel (pictured) “Allen Distinguished Investigators” and awarded them $1.4 million to identify networks of genes controlling the cellular biology of Alzheimer’s disease. Only five research teams were given awards by the Allen Family Foundation to... Read more ...

Defective Protein Found to Cause Rare Parkinson’s-like Disease

Published in the San Francisco Chronicle; 31 August 2015

By David Perlman

When Stanley B. Prusiner, a UCSF neurologist, first proposed that inert proteins he called prions could somehow fold into strange shapes and infect humans with rare diseases of the brain, his idea 30 years ago was widely dismissed as nonsense.

His critics were wrong.

Twenty years later those infectious prions—which Prusiner coined from two words, protein and infection—won him a Nobel prize, and today his Institute for Neurodegenerative Disease has its own building on the medical center’s Mission Bay campus. It’s a scientific hive where researchers, lab techs and medical students labor to understand the many disorders that endanger the human brain and the human nervous system.

Now Kurt Giles, a British-born neurologist at the UCSF Institute, is reporting that he and his colleagues have found that... Read more ...

Innovative genetic approach uncovers target of promising molecule ISRIB

ISRIB, a drug-like molecule that inhibits the integrated stress response, was identified in 2013 in Peter Walter’s lab at UCSF. The integrated stress response is a central pathway in mammalian proteostasis, disruptions to which are believed to be central in many neurodegenerative diseases. When given to mice, ISRIB enhanced memory and learning. In collaboration with the Walter lab, IND faculty Martin Kampmann utilized a functional genomics approach to discover the target of ISRIB. The action of ISRIB depends on eIF2B, a nucleotide exchange factor important for protein production. The team then confirmed that the delta subunit of elF2B is the direct target of ISRIB. This molecular understanding might enable the development of ISRIB into a drug for the treatment of human neurologic diseases.

The study was published in the April 15, 2015... Read more ...