Alzheimer's disease and metals: A review of the involvement of cellular membrane receptors in metallosignalling

Abstract

Alzheimer's disease (AD) is a debilitating form of dementia. The hallmark protein associated with the disease is the amyloid beta (A) peptide. Aggregation of Aβ has been shown to depend on interactions with metals. The recent studies now demonstrate that metals also play additional important roles in the disease process. Consequently, there may be benefit from modulating metal homeostasis. However, the role and subcellular location of metals within neurons is not well understood. There is growing evidence to suggest that metals can act at the site of cellular membrane receptors and affect cellular signaling by modulating the signal transduction of those receptors. The glutamatergic and cholinergic receptor systems, both well-known neurotransmitter systems affected in AD, have well-documented metal interactions, as do the tropomyosin-receptor kinase (Trk) family of receptors and the epidermal growth factor (EGF) receptor. In this paper, the metal interactions with these membrane receptor systems will be explored and thus the potential for membrane receptors as an intervention point in AD will be assessed. © 2011 Pavithra C. Amadoruge and Kevin J. Barnham.