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1. Beta-amyloid peptides enhances alpha-synuclein accumulation and neuronal deficits in a transgenic mouse model linking Alzheimer's disease and Parkinson's disease E Masliah, E Rockenstein, I Veinbergs, Y Sagara, M Mallory, M Hashimoto, L Mucke Proc Nat Acad Sci USA 2001;98:12245-12250 Beta-amyloid, the protein fragment implicated in Alzheimer's disease, promotes alpha-synuclein aggregation and accelerates parkinsonian symptoms in transgenic models of Parkinson's disease, according to this study. Mice transgenic for mutant human alpha-synuclein, mutant human beta-amyloid protein precursor, or both, were followed over time for onset and severity of movement disorders and cognitive impairment. The interaction of the two proteins was also examined in a cell-free system and cell culture. Results showed: --amyloid promoted the aggregation of synuclein in both the cell-free system and cell culture. In contrast, synuclein did not accelerate formation of amyloid plaques. --At six months, the double transgenic mice had significantly poorer motor performance compared to control mice as determined on the rotarod test, while neither of the single transgenic mice were significantly affected. By 12 months, performance of the synuclein transgenic mice had decline to match that of the double transgenic mice, with no decline in the amyloid transgenic mice. --At six months, both the amyloid transgenic mice and double transgenic mice showed impaired spatial memory compared to control and synuclein transgenic mice, as determined in a water maze test. --An age-dependent loss of cholinergic neurons was found in all three transgenic mice, but not in controls, with the greatest loss in the double transgenics. Double transgenic mice also had significantly more synuclein-positive inclusions than single transgenic mice. The authors conclude, "Our study demonstrates that [alpha-synuclein and beta-amyloid precursor protein] have distinct, as well as convergent, pathogenic effects on the integrity and function of the brain…They help explain the clinical observation that the Lewy-body variant of Alzheimer's disease causes a more rapid decline that pure Alzheimer's disease." 2. Pesticides directly accelerate the rate of alpha-synuclein fibril formation: A possible factor in Parkinson's disease VN Uversky, J Li, AL Fink FEBS Letters 2001;500:105-108 Rotenone, paraquat, dieldrin and diethyldithiocarbamate (DDC) accelerate aggregation of alpha-synuclein in cell-free systems, according to this report. A solution of purified synuclein was mixed with each pesticide and fibrillization was monitored. Fibril formation was influenced by concentration, stir rate, and other parameters, and was greatest for DDC and least for rotenone. Spectroscopic and visual studies confirmed the effect was due to a conformation change consistent with formation of beta sheets, and both fibrils and amorphous deposits were formed. The authors note, "It remains to be determined how quickly alpha-synuclein fibrils will form with the concentrations of alpha-synuclein and pesticides found in neurons. The concentration of both alpha-synuclein and pesticide in the dopaminergic neurons is unknown at present." Copyright 2001 WE MOVE Editor: Richard Robinson ([log in to unmask]) This service is provided free of charge to the Internet community, courtesy of WEMOVE.org. This document may be freely redistributed by email only in its unedited form. We encourage you to share it with your colleagues. Patient subscribers: Information presented in the above article(s) should not in any way be interpreted as medical advice. Please contact your physician if you have questions about the information presented by the E-MOVE news service or archives. It is not possible, nor is it appropriate for WE MOVE to respond directly to questions regarding medical management, including diagnosis and treatment. E-MOVE archives, plus information on subscribing, are available at http://www.wemove.org/emove. To unsubscribe, send an e-mail to [log in to unmask], with "unsubscribe e-move" in the message body. E-MOVE is a service of WE MOVE (Worldwide Education and Awareness for Movement Disorders) 204 West 84th Street New York, NY 10024 TEL 800-437-MOV2 TEL 212-875-8312 FAX 212-875-8389 http://www.wemove.org ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn