Intrinsic disorder in proteins associated with neurodegenerative diseases

Abstract

Neurodegenerative diseases constitute a set of pathological conditions originating from the slow, irreversible and systematic cell loss within the various regions of the brain and/or the spinal cord. Neurodegenerative diseases are proteinopathies associated with misbehavior and disarrangement of a specific protein, affecting its processing, functioning, and/or folding. Many proteins associated with human neurodegenerative diseases are intrinsically disordered; i.e., they lack stable tertiary and/or secondary structure under physiological conditions in vitro. Intrinsically disordered proteins (IDPs) have broad presentation in nature. Functionally, they complement ordered proteins, being typically involved in regulation, signaling and control. Structures and functions of IDPs are intensively modulated by alternative splicing and posttranslational modifications. It is recognized now that nanoimaging offers a set of tools to analyze protein misfolding and self-assembly via monitoring the aggregation process, to visualize protein aggregates, and to analyze properties of these aggregates. The major goals of this review are to show the interconnections between intrinsic disorder and human neurodegenerative diseases and to overview a recent progress in development of novel nanoimaging tools to follow protein aggregation.