HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Development of new treatments for Parkinson's disease in transgenic animal models: a role for beta-synuclein.

Abstract
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.
AuthorsEliezer Masliah, Makoto Hashimoto
JournalNeurotoxicology (Neurotoxicology) Vol. 23 Issue 4-5 Pg. 461-8 (Oct 2002) ISSN: 0161-813X [Print] Netherlands
PMID12428718 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S., Review)
Chemical References
  • Nerve Tissue Proteins
  • SNCA protein, human
  • SNCB protein, human
  • Synucleins
  • alpha-Synuclein
  • beta-Synuclein
Topics
  • Amyloidosis (drug therapy, genetics, metabolism)
  • Animals
  • Animals, Genetically Modified
  • Cell Aggregation
  • Disease Models, Animal
  • Humans
  • Nerve Tissue Proteins (chemistry, genetics, physiology)
  • Parkinson Disease, Secondary (drug therapy, genetics, metabolism)
  • Protein Binding
  • Protein Folding
  • Synucleins
  • alpha-Synuclein
  • beta-Synuclein

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: