Intrinsic Disorder in Proteins Associated with Neurodegenerative Diseases

Abstract

Neurodegenerative diseases constitute a set of pathological conditions originating from the slow, irreversible and systemic cell loss within the various regions of the brain and/or the spinal cord. Depending on the affected region, the outcomes of the neurodegeneration are very broad, starting from the problems with movements and ending with dementia. Neurodegenerative diseases are pro-teinopathies 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. The major goal of this chapter is to uncover intriguing interconnections between intrinsic disorder and human neurodegenerative diseases. 2.1 Neurodegenerative Diseases as Proteinopathies The large class of human neurodegenerative disorders includes many acquired neurological diseases with distinct phenotypic and pathologic expressions, all characterized by the pathological conditions in which cells of the brain and spinal cord are lost. The name for these diseases is derived from a Greek word νρo-, néuro-, "nerval" and a Latin verb d¯ egener¯ are, "to decline" or "to worsen". As neurons are not readily regenerated, their deterioration leads over time to dysfunction and disabilities. Neurodegenerative diseases can be divided into two groups according to their phenotypic effects: (i) Conditions causing problems with movements; and (ii) Conditions affecting memory and leading to dementia. Neurodegeneration is a slow process, which begins long before the patient experiences any symptoms.