Subcellular localization of α-synuclein in primary neuronal cultures: Effect of missense mutations

P. J. McLean, S. Ribich, B. T. Hyman

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Numerous recent observations have implicated α-synuclein in the pathogenesis of several neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, dementia with Lewy bodies and multiple-system atrophy. Two missense mutations in the gene for α-synuclein have been identified in some cases of familial Parkinson's disease and it is thought that these may disrupt the normal structure of the protein and thus promote aggregation into Lewy body filaments. Here, we examine the subcellular localization of α-synuclein in primary cortical neurons maintained in a monolayer culture. The protein has widespread expression throughout neurons, including the nucleus, and has a discete localization in the neurites of more mature neurons, reminiscent of synaptic specializations. Interestingly, in a subpopulation of cortical neurons transfected at 13 days in vitro, we find that α-synuclein appears to aggregate into distinct punctate inclusions in the cytoplasm and proximal neurites. Unlike Lewy bodies, these structures are not ubiquitin positive. These regions of α-synuclein accumulation are observed following transfections with wild-type, Ala30Pro or Ala53Thr α-synuclein; neither mutation alters their frequency.

Original languageEnglish (US)
Pages (from-to)53-63
Number of pages11
JournalJournal of Neural Transmission, Supplement
Issue number58
DOIs
StatePublished - Jan 1 2000

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry

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