Genetically encoded biosensors of metabolic function for the study of neurodegeneration, a review and perspective

Nervous system tissue is the most metabolically active in the body and neurons are the primary consumers of oxygen and metabolites in nervous tissue. Many processes support neuronal metabolism, and dysregulation of these processes or intrinsic neuronal metabolism is often tied to neurodegenerative diseases. While many techniques are available to query metabolic function and disease (e.g. Seahorse XF, histology, immunostaining), almost all of these approaches are destructive and few offer cellular resolution. However, genetically encoded biosensors can optically measure metabolic features in any tissue with optical access. Biosensors represent an approach to non-destructively monitor metabolic components and regulatory signaling repeatedly over time in intact tissues. In this review, we discuss the application of genetically encoded biosensors that measure metabolites and metabolic processes as applied to studies of neurodegeneration.