科研之友
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摘要
Genetic, biochemical, and animal model studies strongly suggest a central role for alpha-synuclein in the pathogenesis of Parkinson's disease. alpha-synuclein lacks a signal peptide sequence and has thus been considered a cytosolic protein. Recent data has suggested that the protein may be released from cells via a non-classical secretory pathway and may therefore exert paracrine effects in the extracellular environment. However, proof that alpha-synuclein is actually secreted into the brain extracellular space in vivo has not been obtained. We developed a novel highly sensitive ELISA in conjugation with an in vivo microdialysis technique to measure alpha-synuclein in brain interstitial fluid. We show for the first time that alpha-synuclein is readily detected in the interstitial fluid of both alpha-synuclein transgenic mice and human patients with traumatic brain injury. Our data suggest that alpha-synuclein is physiologically secreted by neurons in vivo. This interstitial fluid pool of the protein may have a role in the propagation of synuclein pathology and progression of Parkinson's disease.
- 出版日期2011-7-14
