Angiotensin Converting Enzyme (ACE) expression in microglia reduces amyloid β deposition and neurodegeneration by increasing SYK signaling and endolysosomal trafficking.

Genome-wide association studies (GWAS) have identified many gene polymorphisms associated with an increased risk of developing Late Onset Alzheimer's Disease (LOAD). Many of these LOAD risk-associated alleles alter disease pathogenesis by influencing microglia innate immune responses and lipid metabolism. Angiotensin Converting Enzyme (ACE), a GWAS LOAD risk-associated gene best known for its role in regulating systemic blood pressure, also enhances innate immunity and lipid processing in peripheral myeloid cells, but a role for ACE in modulating the function of myeloid-derived microglia remains unexplored.

Targeted toxins for glioblastoma multiforme: pre-clinical studies and clinical implementation.

Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. GBM is very aggressive due to its poor cellular differentiation and invasiveness, which makes complete surgical resection virtually impossible. Therefore, GBM's invasive nature as well as its intrinsic resistance to current treatment modalities makes it a unique therapeutic challenge.

Flt3L in Combination With HSV1-TK-mediated Gene Therapy Reverses Brain Tumor-induced Behavioral Deficits.

Glioblastoma multiforme (GBM) is an invasive and aggressive primary brain tumor which is associated with a dismal prognosis. We have earlier developed a macroscopic, intracranial, syngeneic GBM model, in which treatment with adenoviral vectors (Ads) expressing herpes simplex virus type 1 thymidine kinase (HSV1-TK) plus ganciclovir (GCV) resulted in survival of ∼20% of the animals. In this model, treatment with Ads expressing Fms-like tyrosine kinase 3 ligand (Flt3L), in combination with Ad-HSV1-TK improves the survival rate to ∼70% and induces systemic antitumor immunity.

Intracranial glioblastoma models in preclinical neuro-oncology: neuropathological characterization and tumor progression.

Although rodent glioblastoma (GBM) models have been used for over 30 years, the extent to which they recapitulate the characteristics encountered in human GBMs remains controversial. We studied the histopathological features of dog GBM and human xenograft GBM models in immune-deficient mice (U251 and U87 GBM in nude Balb/c), and syngeneic GBMs in immune-competent rodents (GL26 cells in C57BL/6 mice, CNS-1 cells in Lewis rats). All GBMs studied exhibited neovascularization, pleomorphism, vimentin immunoreactivity, and infiltration of T-cells and macrophages.