Proteins aggregation and human diseases

4th International Workshop on Statistical Physics and Mathematics for Complex Systems

物理学;数学

Hu, Chin-Kun^1

Institute of Physics of Academia Sinica, Taipei

11529, Taiwan^1

关键词: Aggregation rate;    Alzheimer's disease;    Chinese medicines;    Huntington's disease;    Lower temperatures;    Parkinson's disease;    Protein aggregation;    Protein sequences;   

Others  :  https://iopscience.iop.org/article/10.1088/1742-6596/604/1/012009/pdf
DOI  :  10.1088/1742-6596/604/1/012009

来源: IOP

【 摘 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), frontotemporallobar degeneration, etc. Such diseases are due to progressive loss of structure or function of neurons caused by protein aggregation. For example, AD is considered to be related to aggregation of Aβ40 (peptide with 40 amino acids) and Aβ42 (peptide with 42 amino acids) and HD is considered to be related to aggregation of polyQ (polyglutamine) peptides. In this paper, we briefly review our recent discovery of 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 quickly. 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 models were 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 medicine was found for Alzheimer's disease.