%0 Journal Article
%T Quantitative connection between polyglutamine aggregation kinetics and neurodegenerative process in patients with HuntingtonĄ¯s disease
%A Keizo Sugaya
%A Shiro Matsubara
%J Molecular Neurodegeneration
%D 2012
%I BioMed Central
%R 10.1186/1750-1326-7-20
%X Using polyQ-length as an index, these procedures enabled us for the first time to establish a quantitative connection between aggregation kinetics and disease process, including onset and the rate of progression. Although the complexity of disease process in HD, the time course of striatal neurodegeneration can be precisely predicted by the mathematical model in which neurodegeneration occurs by different mechanisms for the initiation and progression of disease processes. Nucleation is sufficient to initiate neuronal loss as a series of random events in time. The stochastic appearance of nucleation in a cell population acts as the constant risk of neuronal cell damage over time, while elongation reduces the risk by nucleation in proportion to the increased extent of the aggregates during disease progression.Our findings suggest that nucleation is a critical step in gaining toxic effects to the cell, and provide a new insight into the relationship between polyQ aggregation and neurodegenerative process in HD.
%K HuntingtonĄ¯s disease
%K Polyglutamine aggregation
%K SCA3
%K Stochastic kinetics model
%K Cumulative damage
%K One-hit model
%K Nucleated growth polymerization
%K Nucleation
%K Elongation
%U http://www.molecularneurodegeneration.com/content/7/1/20/abstract