While neurodegenerative disorders and epilepsy are widespread and costly diseases, current treatment options are limited and primarily target symptoms, rather than causes. Metabolic stress is a feature common to many NDDs an epilepsies. However, the mechanisms linking impairments in energy supply and utilization to neuropathology are unclear. We suggest that impaired neuronal energy homeostasis is a primary reason for the high seizure susceptibility in AD and epileptic patients, and the impaired synaptic plasticity in AD. Metabolic failure leads to abnormal neuronal signaling,resulting in an energy deficit, which triggers further aberrant neuronal activity, in a pathological, positive feedback loop. This vicious cycle can however be interrupted by the timely supply of an appropriate alternative energy source e.g., ketone bodies. In this project we will elucidate the mechanisms of neuronal metabolic protection in the developing and mature brains, in order to provide a rational basis for the treatment of NDDs and epilepsies.