Diseases protein misfolding causing

Protein misfolding is most commonly caused by a gene mutation, which produces an altered protein. An example of this is the amyloid protein that spontaneously aggregates in many degenerative diseases, for example, Alzheimer disease. 

The misfolded form, scrapie, results in a class of disease called spongiform encephalopathies, e.g., mad cow disease. Unlike other diseases caused due to protein misfolding, prion diseases are infectious. The infecting agent is the misfolded protein. Prionogenic diseases are transmitted across the species barriers, from cow to sheep to human beings, and are fatal. 

Years of research into protein misfolding diseases such as Alzheimer s disease, Huntington s disease or Creutzfeldt-Jakob disease have clearly established amyloids as disease associated, but not necessarily disease causing. In mammals,... 

Protein misfolding and aggregation are now known to be J/ an important feature of several human diseases. These maladies are referred to as conformational diseases, because they are believed to be caused, at least in part, by abnormal conformational changes in certain proteins. Prominent examples include Alzheimer s disease and Creutzfeld-Jacob disease. Each is discussed briefly. 

Very little difference is seen in the energy state of the native conformation and a number of other stable conformations that a protein might assume. It appears that the prion protein, the cause of mad cow disease, is a normal cellular protein that has refolded into a different stable conformation with a lower energy state than its normal functional conformation (discussed under Biochemical Comments, later). If misfolded proteins do not precipitate into aggregates, they can be degraded in the cell by proteolytic reactions, or even refolded. 

One of the most fascinating current hypotheses in biochemistry is that misfolded proteins can cause infectious disease. These infectious misfolded proteins are called prions. The best example of a prion is the one thought to be responsible for mad cow disease, which can be transmitted to humans. 

A prion (proteinaceous infectious + on) is a microscopic particle of protein that causes neurological diseases such as Creutzfeldt-Jakob disease (CJD) (Chapter 7). Prions multiply by catalysing the misfold-ing of normal cellular prion proteins (PrP ) into malignant prion forms (e.g. the scrapie prion PrP ) without the participation of DNA and RNA. 

---