Abstract
Down syndrome (DS), trisomy of chromosome 21, is the most common genetic form of intellectual disability. The neuropathology of DS involves multiple molecular mechanisms, similar to AD, including the deposition of beta-amyloid (Aβ) into senile plaques and tau hyperphosphorylationg in neurofibrillary tangles. Interestingly, many genes encoded by chromosome 21, in addition to being primarily linked to amyloid-beta peptide (Aβ) pathology, are responsible for increased oxidative stress (OS) conditions that also result as a consequence of reduced antioxidant system efficiency. However, redox homeostasis is disturbed by overproduction of Aβ, which accumulates into plaques across the lifespan in DS as well as in AD, thus generating a vicious cycle that amplifies OS-induced intracellular changes. The present review describes the current literature that demonstrates the accumulation of oxidative damage in DS with a focus on the lipid peroxidation by-product, 4-hydroxy-2-nonenal (HNE). HNE reacts with proteins and can irreversibly impair their functions. We suggest that among different post-translational modifications, HNE-adducts on proteins accumulate in DS brain and play a crucial role in causing the impairment of glucose metabolism, neuronal trafficking, protein quality control and antioxidant response. We hypothesize that dysfunction of these specific pathways contribute to accelerated neurodegeneration associated with AD neuropathology.
Original language | English |
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Pages (from-to) | 262-269 |
Number of pages | 8 |
Journal | Free Radical Biology and Medicine |
Volume | 111 |
DOIs | |
State | Published - Oct 2017 |
Bibliographical note
Publisher Copyright:© 2017 Elsevier Inc.
Funding
Funders | Funder number |
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NIH National Institute of Child Health and Human Development National Center for Medical Rehabilitation Research | |
Eunice Kennedy Shriver National Institute of Child Health and Human Development | R01HD064993 |
Eunice Kennedy Shriver National Institute of Child Health and Human Development |
Keywords
- 4-hydroxy-2-nonenal
- Alzheimer disease
- Down syndrome
- Lipid peroxidation
- Protein oxidation
- Redox proteomics
ASJC Scopus subject areas
- Biochemistry
- Physiology (medical)