BOSTON, MA A new mouse model developed by Harvard Medical School researchers and reported in the October 30 Neuron may allow scientists for the first time to spotlight two key proteins in a living animal and see how they contribute to the neuronal death and atrophy found in neurodegenerative diseases. The two proteins are dubbed p25 and cyclin-dependent kinase 5 (Cdk5).
"This is an excellent animal model for any therapeutic approach toward p25 and its link to Alzheimer's and similar neurodegenerative diseases," says Li-Huei Tsai, HMS professor of pathology and Howard Hughes Medical Institute associate investigator, the study's lead author. "We know that p25 causes neurodegeneration, and we want to figure out how that mechanism works."
The new model is the latest in Cdk5 research from the lab of Li-Huei Tsai. Over the past nine years, Tsai and her colleagues have defined many of Cdk5's functions and noted the role its usual regulator p35 plays in orienting neuronal migration and growth. Their latest challenge is deciphering how Cdk5 and the pernicious regulator p25 lead to neurodegenerative diseases.
The protein p25 is usually not found in healthy brains, but is formed when a stroke or another oxygen-restricting event cuts p35--a beneficial protein found in healthy brains--to form p25, starting a domino effect that leads to neuronal death and malformation. Once present, p25 activates Cdk5 and alters its normally constructive behavior to kill neurons. To make matters worse, p25 is longer-lived than p35, so it accumulates in the brain and continues to keep Cdk5 active. Overactive Cdk5 and accumulated p25 have been noted in the brain tissue of people with the neurodegenerative diseases Alzheimer's and NiemannPick type C. But the lack of a mouse model prevented researchers from demonstrating in vivo the effects of Cdk5 and p25 in the brain.
Tsai's model exhibits the two characteristics researchers want to study: profound neuronal death Page: 1 2 Related medicine news :1
Contact: John Lacey
Harvard Medical School
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