Polyamine pathway contributes to the pathogenesis of Parkinson disease
Home of Kyle J. Norton for The Better of Living & Living Health Human aging is a biological process, no one can stop, but delay it. It is possible that one person looks younger than his or her biological if one engages in healthy living life style and eating healthily by increasing the intake of good healthy food such as whole grain, fruits, vegetables, beans and legumes, etc. and reducing the consumption of harmful foods, such as saturated fat, trans fat, artificial ingredients, etc.
Spermidine is a naturally occurring polyamine involved in multiple biological processes, including DNA metabolism, autophagy and aging.
Polyamine pathway contributes to the pathogenesis of Parkinson disease
In the study to address this issue of the full complement of molecular pathways contributing to the pathogenesis of Parkinson disease (PD) by taking a broad approach, beginning by using functional MRI to identify brainstem regions differentially affected and resistant to the disease, showed that by relying on these imaging findings, we then profiled gene expression levels from postmortem brainstem regions, identifying a disease-related decrease in the expression of the catabolic polyamine enzyme spermidine/spermine N1-acetyltransferase 1 (SAT1). Next, a range of studies were completed to support the pathogenicity of this finding. First, to test for a causal link between polyamines and α-synuclein toxicity, we investigated a yeast model expressing α-synuclein. Polyamines were found to enhance the toxicity of α-synuclein, and an unbiased genome-wide screen for modifiers of α-synuclein toxicity identified Tpo4, a member of a family of proteins responsible for polyamine transport. Second, to test for a causal link between SAT1 activity and PD histopathology, we investigated a mouse model expressing α-synuclein. DENSPM (N1, N11-diethylnorspermine), a polyamine analog that increases SAT1 activity, was found to reduce PD histopathology, whereas Berenil (diminazene aceturate), a pharmacological agent that reduces SAT1 activity, worsened the histopathology. Third, to test for a genetic link, we sequenced the SAT1 gene and a rare but unique disease-associated variant was identified. Taken together, the findings from human patients, yeast, and a mouse model implicate the polyamine pathway in PD pathogenesis(11).
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Sources
(11) http://www.ncbi.nlm.nih.gov/pubmed/20837543
http://medicaladvisorjournals.blogspot.com
Source: http://medicaladvisorjournals.blogspot.com/2013/08/polyamine-pathway-contributes-to.html
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