METHOD FOR SCREENING FOR ANTI-AMYLOIDOGENIC PROPERTIES AND METHOD FOR TREATMENT OF NEURODEGENERATIVE DISEASE

摘要

The methodologies of the present invention demonstrate that a critical balance between pro- and anti-amyloidogenic molecules exists that regulates amyloid formation and cell death in Alzheimer's disease and Parkinson's disease. beta-Synuclein, the non-amyloidogenic homologue of alpha-synuclein, is a negative modulator of alpha-synuclein and Abeta aggregation, having neuroprotective properties against alpha-synuclein and Abeta neurotoxicity and that beta-synuclein and therapeutic agents derived therefrom block amyloidogenesis and neurodegeneration in vivo. The method of the present invention establishes that beta-synuclein blocks Abeta aggregation either by direct inhibition of Abeta amyloidogenesis or indirectly via either alpha-synuclein or its 35 a.a. NAC region, inferring neuroprotective characteristics within the effected cells. The generation of a transgenic mouse line and a cell system overexpressing alpha-synuclein characterizes the mechanisms by which beta-synuclein blocks alpha-synuclein and Abeta aggregation and that this mechanism offers protection to the cell against amyloid formation as seen in the pathologies of Alzheimer's disease and Parkinson's disease.