Molecular pathology of lewy body diseases

Katrin Beyer, Montserrat Domingo-Sàbat, Aurelio Ariza

Research output: Contribution to journalReview articleResearchpeer-review

91 Citations (Scopus)

Abstract

Lewy body diseases are characterized by the presence of Lewy bodies, alpha- synuclein(AS)-positive inclusions in the brain. Since their main component is conformationally modified AS, aggregation of the latter is thought to be a key pathogenic event in these diseases. The analysis of inclusion body constituents gives additional information about pathways also involved in the pathology of synucleinopathies. Widespread mitochondrial dysfunction is very closely related to disease development. The impairment of protein degradation pathways, including both the ubiquitin-proteasome system and the autophagy-lysosome pathway also play an important role during the development of Lewy body diseases. Finally, differential expression changes of isoforms corresponding to genes primarily involved in Lewy body formation point to alternative splicing as another important mechanism in the development of Parkinson's disease, as well as dementia with Lewy bodies. The present paper attempts to give an overview of recent molecular findings related to the pathogenesis of Lewy body diseases.
Original languageEnglish
Pages (from-to)724-745
JournalInternational Journal of Molecular Sciences
Volume10
Issue number3
DOIs
Publication statusPublished - 1 Mar 2009

Keywords

  • Alpha- Synuclein
  • Alternative splicing
  • Dementia with Lewy bodies
  • Differential isoform expression
  • Lewy body diseases
  • Mitochondrial dysfunction
  • Molecular chaperones
  • Parkinson disease
  • Proteosomal dysfunction

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