abstract |
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. β-Synuclein, the non-amyloidogenic homologue of α-synuclein, is a negative modulator of α-synuclein and Aβ aggregation, having neuroprotective properties against α-synuclein and Aβ neurotoxicity and that β-synuclein and therapeutic agents derived therefrom block amyloidogenesis and neurodegeneration in vivo. The method of the present invention establishes that β-synuclein blocks Aβ aggregation either by direct inhibition of Aβ amyloidogenesis or indirectly via either α-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-free system overexpressing α-synuclein characterizes the mechanisms by which β-synuclein blocks α-synuclein and Aβ 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. |