Neuronal death in
Parkinson's disease (PD), one of the most common
neurodegenerative disorders in the adult and aging population is probably caused by misfolding of synaptic
proteins such as
alpha-synuclein. Although, some treatments are currently available to control some of the symptoms of PD, none of these approaches directly addresses the mechanisms of disease. With the advent of new experimental animal models for this disorder, the potential for development and discovery of new treatment has been significantly bolstered. Among them, overexpression of
alpha-synuclein results in motor deficits. dopaminergic loss and formation of inclusion bodies. Co-expression of mutant
amyloid precursor
protein, accelerates
alpha-synuclein aggregation and enhances the neurodegenerative pathology in these mice, providing a unique model where to investigate the interactions between Abeta1-42 and
alpha-synuclein and to develop treatments for combined
Alzheimer's disease and PD. Development of anti-parkinsonian treatments based on these models includes: (i) anti-aggregation or pro-degradation compounds, (ii) neuroprotective compounds, and (iii) neurotrophic agents. Among them, we characterized
beta-synuclein, the non-amyloidogenic homologue of
alpha-synuclein, as an inhibitor of aggregation of
alpha-synuclein. Our results raise the intriguing possibility that
beta-synuclein might be a natural negative regulator of
alpha-synuclein aggregation, and that a similar class of endogenous factors might regulate the aggregation state of other molecules involved in neurodegeneration. Such an anti-amyloidogenic property of
beta-synuclein might also provide a novel strategy for the treatment of
neurodegenerative disorders.