The triple power of D-3: Protein intrinsic disorder in degenerative diseases

This review is an update of an article published four years ago (Uversky V.N. (2009) Intrinsically disordered proteins in neurodegenerative diseases: another illustration of the D-2 concept. Frontiers in Bioscience 14, 5188-5238). The major goal of this review is to show the interconnections between intrinsically disordered proteins (IDPs) and human neurodegeneration. This brings to existence a new D-3 concept: protein intrinsic Disorder in neuroDegenerative Diseases. An important aspect of the D-3 concept is that it deals with three D-3' s, emphasizing that intrinsically Disordered proteins are abundantly found in various neuroDegenerative Diseases (the first D-3), that these IDPs provoke neuroDegeneration due to their Dysfunctionality (the second D-3), and that neuroDegeneration-related IDPs are often controlled by other Disordered proteins (the third D-3).