In neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases, neurons may die by a form of programmed cell death called apoptosis. A major effort in the Cellular and Molecular Neurosciences section of the Laboratory of Neurosciences is aimed at establishing what triggers apoptosis in neurodegenerative disorders and how neuronal degeneration might be prevented by targeting specific molecular events in the process of apoptosis. We have found that a protein called p53 is involved in the death of neurons in experimental models of Alzheimer's, Parkinson's and Huntington's diseases. Novel specific inhibitors of p53 were developed and several lead agents were shown to be effective in animal models of stroke and Parkinson's disease. In other studies we established important roles for potassium ion fluxes in the pathogenesis of neuronal degeneration in models of stroke. A drug called diazoxide that opens mitochondrial potassium channels was neuronprotective in models of stroke. We have also established roles for brain-derived neurotrophic factor (BDNF) in preventing the apoptosis of neurons produced from stem cells in the hippocampus, a finding that suggests the possibility of increasing the capacity of the brain to replace lost and damaged neurons.
| Gleichmann, Marc; Zhang, Yongqing; Wood 3rd, William H et al. (2012) Molecular changes in brain aging and Alzheimer's disease are mirrored in experimentally silenced cortical neuron networks. Neurobiol Aging 33:205.e1-18 |
| Gong, Eun Ji; Park, Hee Ra; Kim, Mi Eun et al. (2011) Morin attenuates tau hyperphosphorylation by inhibiting GSK3?. Neurobiol Dis 44:223-30 |
| Stutzmann, Grace E; Mattson, Mark P (2011) Endoplasmic reticulum Ca(2+) handling in excitable cells in health and disease. Pharmacol Rev 63:700-27 |
| Yoon, Jeong Seon; Lee, Jong-Hwan; Son, Tae Gen et al. (2011) Pregabalin suppresses calcium-mediated proteolysis and improves stroke outcome. Neurobiol Dis 41:624-9 |
| Romberg, Carola; Mattson, Mark P; Mughal, Mohamed R et al. (2011) Impaired attention in the 3xTgAD mouse model of Alzheimer's disease: rescue by donepezil (Aricept). J Neurosci 31:3500-7 |
| Bruestle, Daniel A; Cutler, Roy G; Telljohann, Richard S et al. (2009) Decline in daily running distance presages disease onset in a mouse model of ALS. Neuromolecular Med 11:58-62 |
| Mattson, Mark P; Ashery, Uri (2009) No more brain tangles with DeltaNp73. Trends Biochem Sci 34:6-8 |
| Mattson, Mark P; Wan, Ruiqian (2008) Neurotrophic factors in autonomic nervous system plasticity and dysfunction. Neuromolecular Med 10:157-68 |
| Liu, Manchang; Liang, Yideng; Chigurupati, Srinivasulu et al. (2008) Acute kidney injury leads to inflammation and functional changes in the brain. J Am Soc Nephrol 19:1360-70 |
| Wilson 3rd, David M; Mattson, Mark P (2007) Neurodegeneration: nicked to death. Curr Biol 17:R55-8 |
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