From redox proteomics to clinical practice: Search for therapeutic targets

Alzheimer disease (AD) is the most common form of dementia in the elderly population, characterized by a gradual deterioration of memory and other cognitive functions. The major pathological characteristics of AD brains are the presence of senile plaques, made of amyloid β-peptide (Aβ), neurofibrillary tangles, composed of hyperphosphorylated tau protein, and neuronal loss. Among putative mechanisms responsible of neurodegeneration, several studies demonstrated the role of oxidative stress as an important factor contributing to the initiation and progression of AD. If from one side disruption of redox balance and increased production of free radicals are likely to be related to mitochondria dysfunction and/or aberrant accumulation of misfolded proteins, on the other side the abnormal accumulation of Aβ and tau proteins appears to promote the redox imbalance. In addition, evidence has suggested that oxidative stress may augment the production and aggregation of Aβ and facilitate the phosphorylation and polymerization of tau, thus forming a vicious cycle that promotes the initiation and progression of AD. Taken together, these findings suggest that therapeutic strategies aimed at preventing/reducing oxidative stress-mediated damage may be effective for the treatment of AD and other neurodegenerative disorders.