Genetically modified tyrosine hydroxylase and uses thereof

Chemistry: molecular biology and microbiology – Micro-organism – per se ; compositions thereof; proces of... – Bacteria or actinomycetales; media therefor

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435190, 4353201, 935 14, 935 10, 536 232, C12N 1500, C12N 904

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active

053004361

ABSTRACT:
Modification of the DNA encoding the enzyme tyrosine hydroxylase (TH) resulting in amino acid substitution in one of the first fifty five N-terminal residues, in particular replacing Ser-40 with Tyr or Leu, produced TH variants having substantially increased enzymatic activity upon transfection of suitable host cells. Cells transfected with the variant TH having enhanced enzymatic activity are useful for treating neurological or psychiatric disorders associated with deficient TH or dopamine, in particular Parkinson's disease, by grafting such cells into the brain.

REFERENCES:
Lee et al., J. of Neurochem., vol. 53, No. 4, 1989, pp. 1238-1244.
Campbell et al., J. Biol. Chem. vol. 261, No. 23, Aug. 15, 1986, pp. 10489-10492.
Grima et al., Nature, vol. 326, Apr. 16, 1987, pp. 707-711.

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