From genetics to pathology: tau and alpha-synuclein assemblies in neurodegenerative diseases

The most common degenerative diseases of the human brain are characterized by the presence of abnormal filamentous inclusions in affected nerve cells and glial cells. These diseases can be grouped into two classes, based on t he identity of the major proteinaceous components of the filamentous assemb lies. The filaments are made of either the microtubule-associated protein t au or the protein alpha -synuclein. Importantly, the discovery of mutations in the tau gene in familial forms of frontotemporal dementia and of mutati on in the alpha -synuclein gene in familial forms of Parkinson's disease ha s established that dysfunction of tau protein and alpha -synuclein can caus e neurodegeneration.