Protein misfolding diseases

Protein misfolding diseases

1. Proteopathy

   • Neurodegenerative diseases
     • Huntington's
     • ALS
     • Creutzfeld-Jakob disease
     • Parkinson's
   • Biological prevention
     • PQC
     • Chaperones
       • " Interestingly, the existence of chaperones implies that some proteins have inherently unstable conformations that can "flip" from a functional minimal-energy state to a state that is nonfunctional or even toxic." Nature
   • General susceptability
   • Pathophysiology
     • Amyloids
       • "Misfolded proteins (also called toxic conformations) are typically insoluble, and they tend to form long linear or fibrillar aggregates known as amyloid deposits. " Nature
         • "...the transition from alpha helix to beta sheet is characteristic of amyloid deposits. The abnormal conformational transition from alpha helix to beta sheet exposes hydrophobic amino acid residues and promotes protein aggregation." Nature
     • Tau proteins
     • Energy funnel
       • Multiple low-energy folding states
         • One functional
     • "As we age... ...the delicate balance of the synthesis, folding, and degradation of proteins is perturbed, resulting in the production and accumulation of misfolded proteins that form aggregates" Nature
   • Sources
     • http://www.ncbi.nlm.nih.gov/pubmed/16722804
     • http://www.ncbi.nlm.nih.gov/pubmed/22647474
     • Nature : http://www.nature.com/scitable/topicpage/protein-misfolding-and-degenerative-diseases-14434929
     • Pics
       • Misfolding prot. metabolism
         • http://www.nature.com/scitable/content/ne0000/ne0000/ne0000/ne0000/14463077/f3_dobson_nature02261-f2.2.jpg
     • http://www.neurobiologyofaging.org/article/S0197-4580(00)00160-3/abstract
     • IFLSCIENCE: http://www.iflscience.com/brain/alzheimer-s-memory-disorder-identified
   • Prions: Transmissible spongiform encephalopathies
     • BSE
     • kuru