Protein State Affects Behavior of Alzheimer's Protein

Protein has opposite effects on normal and mutant tau protein

THURSDAY, April 24 (HealthDay News) -- In neurodegenerative diseases such as Alzheimer's disease that involve abnormalities in the tau protein (tauopathies), a tau-regulating protein has opposite effects on tauopathy in mice depending on whether the tau is normal or mutant, according to a study published online April 22 in The Journal of Clinical Investigation.

Jormay Lim, Ph.D., of Harvard Medical School in Boston and colleagues examined how the ability of the prolyl isomerase Pin1 to bind and isomerize the tau protein, which binds and promotes the polymerization of microtubules, is affected by lack of the tau protein or mutations in the tau protein in cells and in mice.

The researchers found that with wild-type tau protein, lack of Pin1 increased tau protein stability and Pin1 overexpression suppressed the tauopathy phenotype in mice. However, with the P301L tau protein mutant, lack of Pin1 decreased tau protein stability and suppressed the tauopathy phenotype in mice, but overexpression of Pin1 worsened the tauopathy phenotype in mice.

"Thus, Pin1 has opposite effects on the tauopathy phenotype depending on whether the tau is WT (wild-type) or a P301L mutant, indicating the need for disease-specific therapies for tauopathies," Lim and colleagues conclude.


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