Details

Autor(en) / Beteiligte

• Siotto, Mariacristina
• Squitti, Rosanna

Titel

Copper imbalance in Alzheimer’s disease: Overview of the exchangeable copper component in plasma and the intriguing role albumin plays

Ist Teil von

• Coordination chemistry reviews, 2018-09, Vol.371, p.86-95

Ort / Verlag

Elsevier B.V

Erscheinungsjahr

2018

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• •Copper concentration and transport in human plasma have a role in Alzheimer disease.•A shift from protein-bound metals to loosely bound occurs in Alzheimer disease brain.•The serum pool of copper not bound to ceruloplasmin is expanded in Alzheimer disease.•Serum albumin plays a pivotal role in copper binding, transport and oxidative cycle.•Glycated albumin can influence and exacerbate copper toxicity in Alzheimer disease. Essential metals are vital elements for human biology. Iron, copper, and zinc are all essential for life. Trace metal dyshomeostasis has been linked to cognitive deterioration and in particular to a disturbance in the regulation of copper (Cu), characterized by an increase in serum Cu not bound to ceruloplasmin (nCp-Cu also known as “free” copper). It is thought to play a role in the development of Alzheimer’s disease (AD), the most common form of dementia. Copper homeostasis is finely regulated in our bodies and the expansion of exchangeable nCp-Cu is symptom of the breakdown of this homeostasis, which affects myriad biological pathways. If not structurally bound to enzymes or coordinated by proteins, copper generates free radicals via Haber-Weiss and Fenton reactions. Human Serum Albumin (HSA) is the most abundant serum protein and the main protein exchanging copper in the nCp-Cu pool. Copper coordinated by HSA is in equilibrium with copper coordinated by other small copper chelators circulating in the blood stream in a dynamic and exchangeable manner dependent on environmental osmolarity, oxidation state, pH and compounds’ functions. Albumin is susceptible to glycation starting from Maillard reaction, carbohydrates, in particular glucose, form advanced glycation end-products (AGEs). AGE-albumin is one of this products. Free radicals and free metals in circulation accelerate this cross-linking of protein with carbohydrates. Modified albumins are also significantly less effective than native forms in avoiding the aggregation of Aβ, the main component of the amyloid plaques in the AD brain. The current review aims to provide insight into the coordination chemistry of copper in plasma with a special glance toward the exchangeable copper coordinated by albumin, to explore how aberrant regulations of this interaction are linked to the aetiology of AD.