Calcium alterations in Alzheimer's disease: Pathophysiology, models and therapeutic opportunities

Abstract

Calcium plays a pivotal role in mediating many important biological functions. The intracellular calcium concentration is tightly regulated by a variety of systems and mechanisms. Calcium is sequestered by various organelles such as mitochondria and/or endoplasmic reticulum and extruded across the plasma membrane by energy-dependent transport systems. Different Ca2+-binding proteins are also involved in these processes. Alterations in calcium homeostasis might be critically implicated in brain aging and in the neuropathology of Alzheimer's disease (AD). In fact, one of the postulated mechanisms of β-amyloid toxicity seems to involve a Ca2+ dysregulation accompanied with enhanced vulnerability to excitotoxic stimuli. Although brain characteristic lesions - plaques and tangles - constitute the hallmarks of AD, accumulated evidence suggests the systemic feature of this disease. Therefore peripheral cell lines may represent a useful approach to explore the cellular pathophysiology of AD, including calcium alterations and associated phenomena.