Glucose/mitochondria in neurological conditions.

Impairments of glucose and mitochondrial function are important causes of brain dysfunction and therefore of brain disease. Abnormalities have been found in association with disease of the nervous system in most of the components of glucose/mitochondrial metabolism. In many, molecular genetic abnormalities have been defined. Brain glucose oxidation is abnormal in common diseases of the nervous system, including Alzheimer disease and other dementias, Parkinson disease, delirium, probably schizophrenia and other psychoses, and of course cerebrovascular disease. Defects in a single component and even a single mutation can be associated with different clinical phenotypes. The same clinical phenotype can result from different genotypes. The complex relationship between biological abnormality in brain glucose utilization and clinical disorder is similar to that in other disorders that have been intensively studied at the genetic level. Genes for components of the pathways of brain glucose oxidation are good candidate genes for disease of the brain. Preliminary data support the proposal that treatments to normalize abnormalities in brain glucose oxidation may benefit many patients with common brain diseases.