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- Title
Mechanisms of Nitrosamine-Mediated Neurodegeneration: Potential Relevance to Sporadic Alzheimer's Disease.
- Authors
De la Monte, Suzanne M.; Tong, Ming
- Abstract
Streptozotocin (STZ) is a nitrosamine-related compound that causes Alzheimer's disease (AD)-type neurodegeneration with cognitive impairment, brain insulin resistance, and brain insulin deficiency. Nitrosamines and STZ mediate their adverse effects by causing DNA damage, oxidative stress, lipid peroxidation, pro-inflammatory cytokine activation, and cell death, all of which occur in AD. We tested the hypothesis that exposure to N-nitrosodiethylamine (NDEA), which is widely present in processed/preserved foods, causes AD-type molecular and biochemical abnormalities in central nervous system (CNS) neurons. NDEA treatment of cultured post-mitotic rat CNS neurons (48 h) produced dose-dependent impairments in ATP production and mitochondrial function, and increased levels of 8-hydroxy-2'-deoxyguanosine, 4-hydroxy-2-nonenal, phospho-tau, amyloid-β protein precursor-amyloid-β (AβPP-Aβ), and ubiquitin immunoreactivity. These effects were associated with decreased expression of insulin, insulin-like growth factor (IGF)-I, and IGF-II receptors, and choline acetyltransferase. Nitrosamine exposure causes neurodegeneration with a number of molecular and biochemical features of AD including impairments in energy metabolism, insulin/IGF signaling mechanisms, and acetylcholine homeostasis, together with increased levels of oxidative stress, DNA damage, and AβPP-Aβ immunoreactivity. These results suggest that environmental exposures and food contaminants may play critical roles in the pathogenesis of sporadic AD.
- Subjects
NITROSOAMINES; ALZHEIMER'S disease; OXIDATIVE stress; INSULIN-like growth factor-binding proteins; CHOLINE; COGNITION disorders
- Publication
Journal of Alzheimer's Disease, 2009, Vol 17, Issue 4, p817
- ISSN
1387-2877
- Publication type
Article
- DOI
10.3233/JAD-2009-1098