| 概 要 |
Many human diseases and the death of most supercentenarians are related to protein aggregation. Neurodegenerative diseases include Alzheimer's disease (AD), Huntington's disease (HD)，Parkinson's disease (PD), frontotemporal lobar degeneration, etc.
Such diseases are due to progressive loss of structure or function of neurons caused by protein aggregation. For example, AD is c onsidered to be related to aggregation of Aβ40 and Aβ42 (protein with 42 amino acids) and HD is considered to be related to aggregation of polyQ (polyglutamine) peptides. In this talk, I briefly review our recent discovery on key factors for protein aggregation. We used a lattice model to study the aggregation rates of proteins and found that the probability for a protein sequence to appear in the conformation of the aggregated state can be used to determine the temperature at which proteins can aggregate most easily . We used molecular dynamics and simple models of polymer chains to study relaxation and aggregation of proteins under various conditions and found that when the bending-angle dependent and torsion-angle dependent interactions are zero or very small, then protein chains tend to aggregate at lower temperatures. All atom model was used to identify a key peptide chain for the aggregation of insulin chains and to find that two polyQ chains prefer anti-parallel conformation. It is pointed out that in many cases, protein aggregation does not result from protein mis-folding.
A potential drug from Chinese herb is found for Alzheimer's diseass.
References
[1] M. S. Li, N. T. Co, G. Reddy, C. -K. Hu, J. E. Straub, and D. Thirumalai, Factors Governing Fibrillogenesis of Polypeptide Chains Revealed by Lattice Models, Phys. Rev. Lett. 105, 218101 (2010).
[2] W. -J. Ma, and C. -K. Hu, J. Phys. Soc. Jpn. 79, 054001 (2010).
[3] W. -J. Ma, and C. -K. Hu, J. Phys. Soc. Jpn. 79, 104002 (2010).
[4] N. T. Co, C.-K. Hu and M. S. Li, J. Chem. Phys. 138, 185101 (2013).
[5] H. -L. Chiang, S. T. Ngo, C. -J. Chen, C. -K. Hu, M. S. Li, Plos One, 8, 65358 (2013).
[6] M. H. Viet, C. -Y. Chen, C. -K. Hu, Y. -R. Chen, and M. S. Li, Plos One 8, 79151 (2013).
[7] H. -L. Chiang, C. J. Chen, H. Okumura, C. -K. Hu, J. Comp. Chem., 35, 1430-1437 (2014).
[8] C. -K. Hu, Journal of Physics: Conference Series, 604, 012009 (2015).
*Seminar talk at IMS in Okazaki, Japan on 27 November 2015
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