The present invention provides a method of screening for compounds which affect the processing of EphA4 by .gamma.-secretase, comprising the following steps: (i) contacting a first biological composition containing .gamma.-secretase or a biologically active fragment thereof with a second biological composition containing EphA4 in the presence and absence of a candidate compound; (ii) measuring the cleavage of the EphA4 in the presence and absence of the candidate compound; (iii) selecting those candidate compounds which affect the cleavage of the EphA4 by .gamma.-secretase; and (iv) identifying the candidate compounds selected in step (iii) as compounds which affect the processing of EphA4 by .gamma.-secretase.