The Anticholinesterase Phenserine and Its Enantiomer Posiphen as 5′Untranslated-Region-Directed Translation Blockers of the Parkinson’s Alpha Synuclein Expression
Joint Authors
Mikkilineni, Sohan
Greig, Nigel H.
Balliedier, Amelie
Cahill, Catherine M.
Rogers, Jack T.
Cantuti-Castelvetri, Ippolita
Source
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-03-21
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
There is compelling support for limiting expression of alpha-synuclein (α-syn) in the brains of Parkinson’s disease (PD) patients.
An increase of SNCA gene copy number can genetically cause familial PD where increased dose of this pathogenic protein correlates with severity of symptoms (triplication of the SNCA gene causes dementia in PD patients).
Gene promoter polymorphisms were shown to increase α-synuclein expression as a risk for PD.
Cholinesterase inhibitors can clinically slow cognitive decline in the later stages of PD etiology similar to their widespread use in Alzheimer’s disease (AD).
Pertinent to this, we identified that the well-tolerated anticholinesterase, phenserine, blocked neural SNCA mRNA translation and tested for targeting via its 5′untranslated region (5′UTR) in a manner similar to its action to limit the expression of the AD-specific amyloid precursor protein (APP).
Posiphen, its better-tolerated (+) enantiomer (devoid of anticholinesterase action), repressed neural α-synuclein translation.
Primary metabolic analogs of posiphen were, likewise, characterized using primary fetal neurons grown ex vivo from the brains of Parkinson’s transgenic mice expressing the human SNCA gene.
American Psychological Association (APA)
Mikkilineni, Sohan& Cantuti-Castelvetri, Ippolita& Cahill, Catherine M.& Balliedier, Amelie& Greig, Nigel H.& Rogers, Jack T.. 2012. The Anticholinesterase Phenserine and Its Enantiomer Posiphen as 5′Untranslated-Region-Directed Translation Blockers of the Parkinson’s Alpha Synuclein Expression. Parkinson’s Disease،Vol. 2012, no. 2012, pp.1-13.
https://search.emarefa.net/detail/BIM-1002727
Modern Language Association (MLA)
Mikkilineni, Sohan…[et al.]. The Anticholinesterase Phenserine and Its Enantiomer Posiphen as 5′Untranslated-Region-Directed Translation Blockers of the Parkinson’s Alpha Synuclein Expression. Parkinson’s Disease No. 2012 (2012), pp.1-13.
https://search.emarefa.net/detail/BIM-1002727
American Medical Association (AMA)
Mikkilineni, Sohan& Cantuti-Castelvetri, Ippolita& Cahill, Catherine M.& Balliedier, Amelie& Greig, Nigel H.& Rogers, Jack T.. The Anticholinesterase Phenserine and Its Enantiomer Posiphen as 5′Untranslated-Region-Directed Translation Blockers of the Parkinson’s Alpha Synuclein Expression. Parkinson’s Disease. 2012. Vol. 2012, no. 2012, pp.1-13.
https://search.emarefa.net/detail/BIM-1002727
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1002727