Methods using agonist antibodies to CNS neurite outgrowth modulators

摘要

The invention features a method for promoting neural growth in vivo in the mammalian central nervous system by administering a neural cell adhesion molecule which can overcome inhibitory molecular cues found on glial cells and myelin to promote neural growth. Also featured active fragments, cognates, congeners, mimics, analogs, secreting cells and soluble molecules thereof, as well as antibodies thereto, and DNA molecules, vectors and transformed cells capable of expressing them. The neuroprotective of the agents as well as their ability to promote and effect myelination and remyelination are also disclosed, as are the concomitant benefits that these capabilities confer, in the former instance, with regard to reduction of apoptosis and necrosis, and in the latter instance, the treatment of Parkinsonism, Alzheimer's disease and multiple sclerosis. The invention also includes transgenic mouse lines expressing a neural adhesion molecule in differentiated astrocytes, and cells and tissues derived therefrom. The expression of the neural adhesion molecule enhances neurite outgrowth on central nervous system tissue derived from these transgenic mice. The invention also features methods for enhancing neuronal outgrowth of CNS neurons, for enhancing memory and for increasing synaptic efficacy. Also featured are methods of testing drugs which modulate the effects of the neural adhesion molecule, and assay systems suitable for such methods.