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L‐3,4‐Dihydroxyphenylalanine Synthesis by Genetically Modified Schwann Cells
Author(s) -
Owens Geoffrey C.,
Johnson Randall,
Bunge Richard P.,
O'Malley Karen L.
Publication year - 1991
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1991.tb02025.x
Subject(s) - dihydroxyphenylalanine , chemistry , neuroscience , biology , biochemistry , dopamine
We have investigated whether Schwann cells can be modified by gene transfer to synthesize L‐3,4‐dihydroxy‐phenylalanine (L‐DOPA), the immediate precursor in the formation of dopamine. By using a retrovirus containing a rat tyrosine hydroxylase (TH) cDNA, we established an immortalized rodent Schwann cell line that stably expressed high levels of TH and secreted L‐DOPA in vitro when supplied with tyrosine and the essential cofactor biopterin. We also infected primary Schwann cells and demonstrated that cells expressing TH secreted L‐DOPA while maintaining their capacity to myelinate neurons in vitro. This study indicates that it may be feasible to utilize autotransplantation of genetically modified Schwann cells to alleviate the movement disorders in Parkinson's disease.