Learn More
In search for the molecular mechanisms underlying the formation of the major dense line in peripheral nerve myelin we investigated mice deficient in the myelin proteins P0 and MBP. In mice lacking both molecules axons were enwrapped by myelin-like processes devoid of the major dense line, while mice deficient in either protein showed, respectively, partial(More)
Cystatin C is an essential secretory cofactor for neurogenesis with potent protease inhibitor activities. Polymorphisms of cystatin C are genetically associated with Alzheimer's disease (AD), and the L68Q mutation causes hereditary cerebral hemorrhage with amyloidosis of the Icelandic type, in which cystatin C and beta-amyloid are colocalized in cortical(More)
Effects of ex vivo GDNF gene delivery on the degeneration of motoneurons were studied in the G1H transgenic mouse model of familial ALS carrying a human superoxide dismutase (SOD1) with a Gly93Ala mutation (Gurney et al., 1994). Retroviral vectors were made to produce human GDNF or E. coli beta-galactosidase (beta-Gal) by transient transfection of the(More)
Mutations in the superoxide dismutase gene 1 (SOD-1) are found in patients with familial amyotrophic lateral sclerosis (FALS). Overexpression of a mutated human SOD-1 gene in mice results in neurodegenerative disease as result of motoneuron loss in lumbar spinal cord (10). Using this mouse model of FALS, we have established a quantitative assay utilizing(More)
Accumulation of the beta-amyloid peptide (Abeta) in the brain is a major pathological hallmark of Alzheimer's disease (AD), leading to synaptic dysfunction, neuronal death, and memory impairment. The levels of neprilysin, a major Abeta-degrading enzyme, are decreased in AD brains and during aging. Because neprilysin cleaves Abeta in vivo, its(More)
Because glucocorticoid excess increases neuronal vulnerability, genetic variations in the glucocorticoid system may be related to the risk for Alzheimer's disease (AD). We analyzed single-nucleotide polymorphisms in 10 glucocorticoid-related genes in a population of 814 AD patients and unrelated control subjects. Set-association analysis revealed that a(More)
The cholesterol-synthesizing enzyme seladin-1, encoded by the Dhcr24 gene, is a flavin adenine dinucleotide-dependent oxidoreductase and regulates responses to oncogenic and oxidative stimuli. It has a role in neuroprotection and is downregulated in affected neurons in Alzheimer's disease (AD). Here we show that seladin-1-deficient mouse brains had reduced(More)
DHCR24/seladin-1, a crucial enzyme in sterol synthesis, is of lower abundance in brain areas affected by Alzheimer's disease. While high levels of DHCR24/seladin-1 exert antiapoptotic function by conferring resistance against oxidative stress, the molecular mechanism for this protective effect is not fully understood. Here we show that DHCR24/seladin-1(More)
We generated defined neuronal loss in hippocampus of genetically identical mice by pilocarpine injections and studied the impact of these seizures on the performance of mice in spatial learning and memory. The numbers of TUNEL-positive degenerating cells paralleled the severity of the seizures. When compared to the numbers found for not-seizured control(More)
Brain beta-amyloid plaques are principal targets for the development of treatments designed to slow the progression of Alzheimer's disease. Intracranial injections of synthetic beta-amyloid peptide (Abeta(42)) in transgenic mice expressing the Alzheimer's disease-causing Swedish APP double mutations increased neuronal levels of neprilysin, a(More)