Adaptive alternative splicing correlates with less environmental risk of parkinsonism

Liat Benmoyal-Segal*, Lilach Soreq, Yoram Ben-Shaul, Shani Ben-Ari, Tehila Ben-Moshe, Sigal Aviel, Hagai Bergman, Hermona Soreq

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Background/Objective: Environmental exposure to anti-acetylcholinesterases (AChEs) aggravates the risk of Parkinsonism due to currently unclear mechanism(s). We explored the possibility that the brain's capacity to induce a widespread adaptive alternative splicing response to such exposure may be involved. Methods: Following exposure to the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), brain region transcriptome profiles were tested. Results: Changes in transcript profiles, alternative splicing patterns and splicing-related gene categories were identified. Engineered mice over-expressing the protective AChE-R splice variant showed less total changes but more splicing-related ones than hypersensitive AChE-S over-expressors with similarly increased hydrolytic activities. Following MPTP exposure, the substantia nigra and prefrontal cortex (PFC) of both strains showed a nuclear increase in the splicing factor ASF/SF2 protein. Furthermore, intravenous injection with highly purified recombinant human AChE-R changed transcript profiles in the striatum. Conclusions: Our findings are compatible with the working hypothesis that inherited or acquired alternative splicing deficits may promote parkinsonism, and we propose adaptive alternative splicing as a strategy for attenuating its progression.

Original languageAmerican English
Pages (from-to)87-98
Number of pages12
JournalNeurodegenerative Diseases
Issue number2
StatePublished - Feb 2012


  • Acetylcholinesterase
  • Alternative splicing
  • Animal models
  • Brain
  • Parkinson's disease


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