The dark side of Alzheimer's disease: unstructured biology of proteins from the amyloid cascade signaling pathway.

The dark side of Alzheimer's disease: unstructured biology of proteins from the amyloid cascade signaling pathway. Cell Mol Life Sci. 2020 Jan 02;: Authors: Gadhave K, Gehi BR, Kumar P, Xue B, Uversky VN, Giri R Abstract Alzheimer's disease (AD) is a leading cause of age-related dementia worldwide. Despite more than a century of intensive research, we are not anywhere near the discovery of a cure for this disease or a way to prevent its progression. Among the various molecular mechanisms proposed for the description of the pathogenesis and progression of AD, the amyloid cascade hypothesis, according to which accumulation of a product of amyloid precursor protein (APP) cleavage, amyloid β (Aβ) peptide, induces pathological changes in the brain observed in AD, occupies a unique niche. Although multiple proteins have been implicated in this amyloid cascade signaling pathway, their structure-function relationships are mostly unexplored. However, it is known that two major proteins related to AD pathology, Aβ peptide, and microtubule-associated protein tau belong to the category of intrinsically disordered proteins (IDPs), which are the functionally important proteins characterized by a lack of fixed, ordered three-dimensional structure. IDPs and intrinsically disordered protein regions (IDPRs) play numerous vital roles in various cellular processes, such as signaling, cell cycle regulation, macromolecular recognition, and promiscuous ...
Source: Cellular and Molecular Life Sciences : CMLS - Category: Cytology Authors: Tags: Cell Mol Life Sci Source Type: research