Neurodegenerative diseases represent a profound medical problem throughout the world. For example, Alzheimer's disease, Parkinson's disease and stroke affect millions of people and have severe physical, psychological and financial consequences for patients and their families. The basic approach of Sidney Strickland's laboratory is to use mouse models of neurological disease to elucidate the molecular mechanisms by which neuronal function is disrupted in these and other neuropathological conditions. Lab members have concentrated on the roles that proteases and extracellular matrix (ECM) proteins play in function and dysfunction in the nervous system. The ECM provides the substrate on which neurons reside, and in addition to having structural importance, also influences neuronal survival and function. Proteases secreted into the extracellular space can modify ECM molecules and thereby affect neurons. The effect of proteases on neurons can be beneficial, contributing to learning, memory and nerve regeneration. However, in pathological situations in which too much protease activity is generated, the effect on neurons can be dramatically deleterious and contribute to neuronal death.