Neurodegenerative disorders are caused by the death and dysfunction of brain cells, but despite a huge worldwide effort, no neuroprotective treatments that slow cell death currently exist. The failure of translation from animal models to humans in the clinic is due to many factors including species differences, human brain complexity, age, patient variability and disease-specific phenotypes. Additional methods are therefore required to overcome these obstacles in neuroprotective drug development. Incorporating target validation using human brain-tissue microarray screening and direct human brain-cell testing at an early preclinical stage to isolate molecules that protect the human brain may be an effective strategy.