Detecting excitotoxicity and neuronal stress in a subject comprises in vitro measurement of phosphodiesterase-4 (PDE4), particularly PDE4B, or detecting the presence of a mutant form of the mRNA for PDE4B, particularly a form that lacks all or part of the 3'-non-coding region. Independent claims are also included for the following: (1) Use of a compound (A) that inhibits or reduces expression or activity of PDE4B for treatment of neurodegenerative diseases; (2) Primers (B) containing 8-20 consecutive residues from the nucleotide region 2384-2869 of a murine PDE4B sequence (S1) or 2461-4068 of a human PDE4B sequence; and (3) Kits for analyzing expression of PDE4. ACTIVITY : Nootropic; Neuroprotective; Antiparkinsonian; Anticonvulsant; Cerebroprotective. Granular neurons from the cerebellum of rats were treated with N-methyl-D-aspartate (i) and serine or kainate (ii), to stimulate excititoxicity. When this treatment was carried out in presence of 50 M pentoxifylline, toxicity was reduced from about 40 to 20% in (i) and from about 30 to 10% in (ii). MECHANISM OF ACTION : Inhibiting expression or activity of PDE4B, which is present at elevated level in pathological nerve tissue.
New molecular target of neurotoxicity