0000000000001086
AUTHOR
Christine Altmann
The Role of SVZ Stem Cells in Glioblastoma
As most common primary brain cancer, glioblastoma is also the most aggressive and malignant form of cancer in the adult central nervous system. Glioblastomas are genetic and transcriptional heterogeneous tumors, which in spite of intensive research are poorly understood. Over the years conventional therapies failed to affect a cure, resulting in low survival rates of affected patients. To improve the clinical outcome, an important approach is to identify the cells of origin. One potential source for these are neural stem cells (NSCs) located in the subventricular zone, which is one of two niches in the adult nervous system where NSCs with the capacity of self-renewal and proliferation resid…
Progranulin overexpression in sensory neurons attenuates neuropathic pain in mice: Role of autophagy
Peripheral or central nerve injury is a frequent cause of chronic pain and the mechanisms are not fully understood. Using newly generated transgenic mice we show that progranulin overexpression in sensory neurons attenuates neuropathic pain after sciatic nerve injury and accelerates nerve healing. A yeast-2-hybrid screen revealed putative interactions of progranulin with autophagy-related proteins, ATG12 and ATG4b. This was supported by colocalization and proteomic studies showing regulations of ATG13 and ATG4b and other members of the autophagy network, lysosomal proteins and proteins involved in endocytosis. The association of progranulin with the autophagic pathway was functionally confi…
Loss of synaptic zinc transport in progranulin deficient mice may contribute to progranulin-associated psychopathology and chronic pain
Affective and cognitive processing of nociception contributes to the development of chronic pain and vice versa, pain may precipitate psychopathologic symptoms. We hypothesized a higher risk for the latter with immanent neurologic diseases and studied this potential interrelationship in progranulin-deficient mice, which are a model for frontotemporal dementia, a disease dominated by behavioral abnormalities in humans. Young naïve progranulin deficient mice behaved normal in tests of short-term memory, anxiety, depression and nociception, but after peripheral nerve injury, they showed attention-deficit and depression-like behavior, over-activity, loss of shelter-seeking, reduced impulse cont…