| First Author | Algarzae N | Year | 2012 |
| Journal | Neuroscience | Volume | 225 |
| Pages | 22-34 | PubMed ID | 22960314 |
| Mgi Jnum | J:192478 | Mgi Id | MGI:5465234 |
| Doi | 10.1016/j.neuroscience.2012.08.057 | Citation | Algarzae N, et al. (2012) Parkin prevents cortical atrophy and Abeta-induced alterations of brain metabolism: (1)(3)C NMR and magnetic resonance imaging studies in AD models. Neuroscience 225:22-34 |
| abstractText | Alzheimer's disease (AD) is a neurodegenerative aging disorder characterized by extracellular Abeta plaques and intraneuronal neurofibrillary tangles. We conducted longitudinal studies to examine the effects of Abeta on brain amino acid metabolism in lentiviral Abeta(1-42) gene transfer animals and transgenic AD mice. We also performed lentiviral parkin gene delivery to determine the effects of Abeta clearance in AD models. Abeta(1-42) activated mTOR signaling, and increased 4E-BP phosphorylation. Abeta(1-42) increased the synthesis of glutamate and aspartate, but not glutamine, leucine and isoleucine, but an increase in leucine and isoleucine levels was concurrent with diminution of neurotransmitters. Additionally, Abeta(1-42) attenuated mitochondrial tricarboxylic acid (TCA) cycle activity and decreased synthesis of its by-products. Glutamate levels increased prior to lactate accumulation, suggesting oxidative stress. Importantly, parkin reversed the effects of Abeta(1-42) on amino acid levels, prevented TCA cycle impairment and protected against glutamate toxicity. Cortical atrophy was observed in aged 3xTg-AD mice, while parkin expression was associated with reduced atrophy. Similarly, Abeta(1-42) resulted in significant cell loss, pronounced astrogliosis and cortical atrophy and parkin reduced astrogliosis and reversed Abeta(1-42) effects on cell loss and cortical atrophy. Taken together these data suggest that parkin prevents amyloid-induced alteration of brain metabolism and may be used as a therapeutic target to limit neuronal loss in AD. |
