Abeta, oxidative stress in Alzheimer disease: Evidence based on proteomics studies

Abstract

The initiation and progression of Alzheimer disease (AD) is a complex process not yet fully understood. While many hypotheses have been provided as to the cause of the disease, the exact mechanisms remain elusive and difficult to verify. Proteomic applications in disease models of AD have provided valuable insights into the molecular basis of this disorder, demonstrating that on a protein level, disease progression impacts numerous cellular processes such as energy production, cellular structure, signal transduction, synaptic function, mitochondrial function, cell cycle progression, and proteasome function. Each of these cellular functions contributes to the overall health of the cell, and the dysregulation of one or more could contribute to the pathology and clinical presentation in AD. In this review, foci reside primarily on the amyloid β-peptide (Aβ) induced oxidative stress hypothesis and the proteomic studies that have been conducted by our laboratory and others that contribute to the overall understanding of this devastating neurodegenerative disease.

Involvement of peroxisome proliferator-activated receptor β/δ (PPAR β/δ) in BDNF signaling during aging and in Alzheimer disease: Possible role of 4-hydroxynonenal (4-HNE)

“…Oxidative damage has been reported in AD mice 17,22,34,35 and lipid peroxidation products, such as 4-HNE, 36 have been found to play an important role in AD-related neurodegeneration. Since 4-HNE has been recognized as an endogenous PPAR β/δ-ligand, 14 the levels of its protein adducts were investigated.…”

Bone-brain crosstalk and potential associated diseases

“…Clinical studies have correlated features of bone metabolism in women with MDD indicating that depressed women had lower bone mass and lower levels of Ocn compared to healthy subjects [120,121]. Moreover, it is known that the antidepressant drugs SSRIs decrease bone mass and increase the risk of fractures, which is consistent with the role of brain-derived serotonin on bone physiology [118,[122][123][124][125]. Interestingly, it was shown that skeletal health in patients with past, but not current history of MDD was comparable to the one of healthy participants, suggesting that bone mass has been normalized after SSRI treatment.…”

Direct Detection of α-Synuclein Dimerization Dynamics: Single-Molecule Fluorescence Analysis

“…Therefore, we speculate that oligomerization propensity depends on the ability to form long-lived dimers, and the high ratio between type 2 and type 1 A30P dimers promotes the oligomerization pathway. Additional dimer stabilization can be provided by oxidation (58,59) and/or nitration (60) processes that could promote protein aggregation in vivo.…”