Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.
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 D² 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 D³ concept: protein intrinsic Disorder in neuroDegenerative Diseases. An important aspect of the D³ concept is that it deals with three D³'s, emphasizing that intrinsically Disordered proteins are abundantly found in various neuroDegenerative Diseases (the first D³), that these IDPs provoke neuroDegeneration due to their Dysfunctionality (the second D³), and that neuroDegeneration-related IDPs are often controlled by other Disordered proteins (the third D³).