Repair Mechanisms in the CNS
As our knowledge of the specific genetic lesions responsible for many neurological disorders increases, we are finding that this information does not necessarily lead to therapeutic advances nor to a better understanding of disease processes. More often than not questions arise asking: What is the relationship between an isolated gene and the pathology and clinical presentation of the disease in question? This is true not only for the most recent genetic discoveries associated with specific neurological disorders, such as SOD and amyotrophic lateral sclerosis, apolipoprotein E and certain types of familial Alzheimer’s disease, and NCP1 and Niemann-Pick disease type C, but also for those inborn errors of metabolism whose causes have been long known, such as Tay-Sachs and other lysosomal storage diseases.
KeywordsEnzyme Replacement Therapy Lysosomal Storage Disease Mevalonic Acid Follow Bone Marrow Transplant Axon Hillock
Unable to display preview. Download preview PDF.
- 3.Purpura DP, Walkley SU (1981) Aberrant neurite and spine generation in mature neurons in the gangliosidoses. In: Rapport M, Gorio A (eds) Gangliosides in neurological and neuromuscular function, development and repair. Raven Press, New York, pp 1–16Google Scholar
- 10.Walkley SU, Siegel DA, Wurzelmann S (1988) Ectopic dendritogenesis and associated synapse formation in swainsonine-induced neuronal storage disease. J Neuroscience 8: 445–457Google Scholar
- 11.Walkley SU, Siegel DA, Dobrenis K (1998) GM2 Ganglioside as a regulator of pyramidal neuron dendritogenesis. In: Hakomori S, Ledeen R, Schneider J et al (eds) Sphingolipids as signalling modulators in the nervous system. Annals of the New York Academy of Sciences 845: 188–199Google Scholar
- 15.Walkley SU, Thrall MA, Dobrenis K et al (1992) Evidence for correction of enzyme defect in CNS neurons in a lysosomal storage disease following bone marrow transplant. Proc Soc Inherited Metabolic DiseasesGoogle Scholar
- 16.Walkley SU, Thrall MA, Dobrenis K (1996) Targeting gene products to the brain and neurons using bone marrow transplantation: a cell-mediated delivery system for therapy of inherited metabolic human disease. In: Lowenstein P, Enquist L (eds) Gene transfer into neurons: Towards gene therapy of neurological disorders. Wiley, New York, pp 275–302Google Scholar
- 17.Dobrenis K (1998) Microglia in cell culture and in transplantation therapy for CNS disease. In: Rosental R, Chiu FC (eds) Methods: A companion to methods in enzymology: Techniques for purification, functional evaluation and transplantation of brain cells. Academic Press, New York, Vol 16, pp 320–344Google Scholar
- 18.Dobrenis K, Finamore PS, Masui R et al (1996) Secretion of lysosomal glycosidases by microglia in culture. Molec Biol Cell 7 [Suppl]: 325aGoogle Scholar
- 19.Siegel DA, Walkley SU, Suzuki K (1982) Characterization of specific a-mannosidase inhibitor from locoweed. Trans Am Soc Neurochem 13: 159Google Scholar
- 23.Bauer D, Muller H, Reich Jet al (1993) Identification of differentially expressed mRNA species by an improved display technique ( DDRT-PCR ). Nucleic Acids Research 21: 4272–4280Google Scholar
- 24.Carlberg M, Dricu A, Blegen H et al (1996) Mevalonic acid is limiting for N-linked glycosylation and translocation of the insulin-like growth factor-1 receptor to the cell surface. Evidence for a new link between 3-hydroxy-3-methylglutaryl-coenzyme A reductase and cell growth. J Biol Chem 271: 17453–17462PubMedCrossRefGoogle Scholar