Protein Misfolding and Degenerative Diseases_Reynaud 2010

Protein Misfolding and Degenerative Diseases_Reynaud 2010 -...

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By: Enrique Reynaud, Ph.D. ( Instituto de Biotecnologia, Universidad Nacional Autonoma de Mexico ) © 2010 Nature Education Protein Misfolding and Degenerative Diseases Figure 1 An error in protein conformation can lead to disease. What are the genetic and molecular causes for incorrectly formed proteins? Current advances in medicine and technology are making our lives longer. Sadly, as our life expectancy increases, the chances of getting a degenerative disease like Alzheimer's, Parkinson's, or diabetes also increases. Why is this? As incredible as it might sound, these diseases are caused not by bacteria or viruses but rather by something conceptually quite simple: incorrect protein folding. Introductory biology courses teach us that proteins are essential for the organism because they participate in virtually every process within the cell . Therefore, if their function is impaired, the consequences can be devastating. As we age, mutations and thermodynamics (as well as some external factors) conspire against us, resulting in the misfolding of proteins. How does this happen? What are the genetic and molecular causes for incorrect folding of proteins, and what is their relationship to aging? Protein Function and Three-Dimensional Structure Our modern understanding of how proteins function comes from almost 200 years of biochemical studies. Biochemistry is the science that studies the chemical processes in living organisms. Using di ! erent experimental models, biochemists demonstrated that most of the cell's chemical reactions and structural components are mediated or supplied by proteins. These experiments revealed that proteins are crucial for proper cell function. Actually the word "protein" comes from the Greek proteios , which means "first" or "foremost," reflecting the importance of these molecules. In 1917 the German chemist Hermann Staudinger proposed that organic molecules such as proteins were organized in polymers, giant molecules made of small-molecule constituents linked together by chemical bonds in long chains. This idea contradicted the prevailing hypothesis, and it took some years for biochemists to accept it. Today researchers know that proteins are long polymers made out of a set of twenty small constituents called amino acids (Figure 1). How are proteins made in the cell? The answer to this question took decades of study and the birth of a new scientific discipline: molecular biology. Many experiments had shown that DNA is the vehicle of genetic information, and that DNA contains the information to make proteins. While discovering that DNA is itself a long polymer made out of four di ! erent types of small molecules called nucleotides, scientists realized that genetic information is transferred from a language system of four letters (nucleotides) in DNA to a language system of twenty (amino acids) in proteins.
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