某变异蛋白质可诱发痴呆

A team of scientists from Japan and the University of California, San Diego School of Medicine have created a new mouse model that confirms that mutations of a protein called beta-synuclein（同型核蛋白） promote neurodegeneration（神经变性） . The discovery creates a potential new target for developing treatments of diseases like Parkinson's and Alzheimer's. The work is published in today's issue of Nature Communications. Lead author is Makoto Hashimoto of the Division of Chemistry and Metabolism²（新陈代谢） , Tokyo Metropolitan³ Institute for Neuroscience, with colleagues including Eliezer Masliah, MD, professor of neurosciences and pathology（病理学） in the UC San Diego School of Medicine, Edward Rockenstein, a research associate in UCSD's Experimental Neuropath Laboratory and Albert R. LaSpada, MD, PhD, professor of cellular⁴ and molecular⁵ medicine, chief of the Division of Genetics in the Department of Pediatrics（小儿科） and associate director of the Institute for Genomic Medicine at UC San Diego.

In 2004, LaSpada discovered mutations in a family afflicted⁶ with（受折磨，患上） a neurological disorder⁷ known as Dementia with Lewy Bodies. DLB is one of the most common types of progressive dementia, combining features of both Alzheimer's and Parkinson's diseases. Lewy bodies are abnormal aggregates⁸（总量，合体） of proteins. There are no known therapies to stop or slow the DLB's progression. There is no cure.

In the 2004 study, LaSpada and colleagues found that mutations of the naturally occurring B-synuclein protein in DLB patients "were strong strongly suggestive of being pathogenic." That is, the mutated protein caused or was a cause of the disease. But the findings were not definitive⁹.

The newly published research describes the creation of a transgenic mouse model that expresses the B-synuclein mutation¹. The mice suffer from neurodegenerative disease, validating¹⁰ LaSpada's earlier work.

"Beta-synuclein is interesting because it is closely related to alpha-synuclein, a protein that can cause Parkinson's disease by being mutated or over-expressed," said LaSpada. "A-synuclein is viewed as central to Parkinson's disease pathogenesis. The question has been: could B-synuclein also promote neurodegeneration because it's similar in its sequence and expression pattern to A-synuclein? This study shows that the answer is yes."

These findings, said LaSpada, establish B-synuclein's links to Parkinson's disease and related disorders¹¹, making it a new and, now, proven target for potential therapies.