Rejuvenating neurons and glia with microbial enzymes.

In: Interaction Between Neurons and Glia in Aging and Disease (J.O. Malva et al., eds.), Springer, 2007, pp. 503-510.

Rejuvenating neurons and glia with microbial enzymes.

de Grey ADNJ.

Abstract

Abstract:

All the major neurodegenerative diseases are characterised by the accumulation of proteinaceous aggregates within neurons. The commonest such condition, Alzheimer’s disease, also features extracellular proteinaceous aggregates (amyloid). The role of these aggregates in the etiology and progression of cognitive impairment is still unclear, but their absence in young adults suggests that their removal would at any rate not be harmful. However, no method for removing the intracellular aggregates in question has yet been developed. Moreover, the engulfment of amyloid by microglia as a result of immunisation may result in loss of microglial function if the amyloid then resists lysosomal digestion. A novel approach to eliminating intracellular aggregates in the brain (and elsewhere) was proposed by the present author in 2002 and has recently attracted enthusiastic support from all relevant specialities, which are unusually disparate. This approach is to isolate bacterial or fungal strains with the capacity to metabolise the recalcitrant aggregates, following which the genes encoding the enzymes responsible would be identified and modified for expression in mammalian cells and targeting to the appropriate subcellular compartment. Delivery could be either of the genes themselves, using somatic gene therapy, or of the enzymes they encode, which would be injected either directly into the brain or into the circulation in conjunction with agents to deliver them across the blood-brain barrier. Ambitious though this approach undoubtedly is, its potential for both the prevention and the treatment of the entire range of neurodegenerative diseases so far exceeds any alternative presently being explored that the case for pursuing it is strong.