title: Release of growth factors by neuronal precursor cells as a treatment for diseases with tau pathology.
abstract: The intraneuronal accumulation of the microtubule associated protein tau in a hyperphosphorylated state and the extracellular deposit of ßamyloid protein constitute the defining neuropathological signature of Alzheimer's disease, the most common type of dementia in ageing Homo sapiens.There is accumulating evidence suggesting that transplantation of embryonic and adult derived neuronal precursor cells (NPCs) has a major role for cell based repair strategies in models of acute and chronic injury. In order to determine whether NPCs could rescue tau related neuronal cell death NPCs were transplanted into the transgenic mouse cortex of transgenic mice expressing human P301S tau protein at 2 month of age and the effect followed 2 and 3 months after transplantation. The results demonstrated that following transplantation mouse NPCs differentiated into astrocytes and exerted a neuroprotective effect. In particular, the expression of ciliary neurotrophic factor, nerve growth factor and glial cell derived neurotrophic factor was increased near the transplanted cells. A nonsignificant increase of brain derived neurotrophic factor expression was instead found in the area of the cortex where neuronal death was rescued.
authors.affiliation: Department of Clinical Neurosciences, University of Cambridge, Cambridge UK. mgs11@cam.ac.uk
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Spillantini
authors.forename: Mariangela
authors.initials: M
authors.lastname: Iovino
authors.forename: Romina
authors.initials: R
authors.lastname: Vuono
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002454:Cell Differentiation; D004195:Disease Models, Animal; D005260:Female; D007839:Functional Laterality; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D058953:Neural Stem Cells / Q000378:metabolism*; D010766:Phosphorylation; D011392:Proline / Q000235:genetics; D012694:Serine / Q000235:genetics; D033581:Stem Cell Transplantation / Q000379:methods*; D024801:Tauopathies / Q000235:genetics / Q000628:therapy*; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D005904:Glial Fibrillary Acidic Protein; D036341:Intercellular Signaling Peptides and Proteins; C054369:MAPT protein, human; D016875:tau Proteins; D012694:Serine; D005680:gamma-Aminobutyric Acid; D011392:Proline