Molecular and cellular biology of synucleins.

Synucleins are small, soluble proteins expressed primarily in neural tissues and certain tumors. The family includes three known proteins: alpha-synuclein, beta-synuclein, and gamma-synuclein. A typical structural feature of synucleins is the presence of a repetitive, degenerative AA motif KTKEGV throughout the first 87 residues and acidic stretches within the C-terminal region. Members of the synuclein family are natively unfolded proteins that are characterized by a high net charge and low hydropathy. The synuclein family recently came into the spotlight when one of its members, alpha-synuclein, was linked both genetically and neuropathologically to Parkinson's disease. It has a role in other neurodegenerative diseases, such as dementia with Lewy bodies, multiple system atrophy, neurodegeneration with brain iron accumulation type 1, and Alzheimer's disease. Interestingly, another member of the family, beta-synuclein, possesses antagonistic properties to alpha-synuclein. The third member of the family, gamma-synuclein, is implicated in different types of cancer, some neurodegenerative diseases and ocular pathology. The involvement of synuclein proteins in the etiology of common human diseases has raised exciting questions and is currently the subject of intense investigation.