The present invention is directed to a target-derived neuronal cholinergic differenciation factor (NCDF), and the therapeutic and diagnostic uses thereof. The invention provides NCDF, and derivatives, analogs, and fragments thereof, pharmaceutical compositions containing the foregoing, as well as anti-NCDF antibodies. The NCDF of the invention is a protein present in extracts of mammalian sweat glands, which exhibits heat and trypsin lability, lack of substantial binding to a heparin-agarose affinity column, an isoelectric point (pI) in the range of approximately 4.8 to 5.2, a non-membrane cellular localization, and an approximate molecular weight in the range of 16 to 32 kilodaltons. The NCDF protein, its derivatives, analogs, and fragments are able to reduce the expression of tyrosine hydroxylase and of total catecholamines, and increase the expression of choline acetyltransferase and vasoactive intestinal peptide (VIP), by sympathetic neurons in cell culture. The NCDF protein, its derivatives, analogs, and fragments, can be used to induce cholinergic activity in neurons. Such proteins, derivatives, analogs and fragments can be administered therapeutically to patients with nervous system damage or diseases where it is desirable to support survival and/or cholinergic differentiation of a number of neuronal types.
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