Chapter category: Neurodegenerative Disease
a-Synuclein Binding Proteins
Chapter authors:
Cytoplasmic inclusions containing a-synuclein in a filamentous form is present in the degenerating cells of several neurodegenerative diseases, the so-called synucleinopathies among whom Parkinson’s disease is a principal member. Moreover, mutations causing single amino acid substitutions in a-synuclein leads to a autosomal dominant forms of Parkinson’s disease that indicates a toxic gain of function. a-synuclein is a small presynaptic protein that is unfolded in its native state. However, in vitro studies have demonstrated its structural promiscuity as it acquires a-helical structure when interacting with lipid bilayers and forms insoluble b-folded amyloid type filaments upon homo-aggregation. During the course of the synucleinopathies, at least two major events occur in its cellular metabolism. First, a large proportion is relocated from the presynapse to axonal and somatodendritic compartments. Second, a structural transition reduces its solubility in conjunction with the accumulation of aggregated/filamentous a-synuclein species. The gain of toxic function is likely contributed to pathological interactions between a-synuclein and cellular constituents and it may be favoured by its abnormal cellular localisation alone or additionally require a structural transition. This review will focus on proteins that interact with a-synuclein and if the interactions exhibits specific structural requirements of a-synuclein.
