Calcium Ions Aggravate Alzheimer's Disease Through the Aberrant Activation of Neuronal Networks, Leading to Synaptic and Cognitive Deficits

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease that is characterized by the production and deposition of β-amyloid protein (Aβ) and hyperphosphorylated tau, leading to the formation of β-amyloid plaques (APs) and neurofibrillary tangles (NFTs). Although calcium ions (Ca²⁺) promote the formation of APs and NFTs, no systematic review of the mechanisms by which Ca²⁺ affects the development and progression of AD has been published. Therefore, the current review aimed to fill the gaps between elevated Ca²⁺ levels and the pathogenesis of AD. Specifically, we mainly focus on the molecular mechanisms by which Ca²⁺ affects the neuronal networks of neuroinflammation, neuronal injury, neurogenesis, neurotoxicity, neuroprotection, and autophagy. Furthermore, the roles of Ca²⁺ transporters located in the cell membrane, endoplasmic reticulum (ER), mitochondria and lysosome in mediating the effects of Ca²⁺ on activating neuronal networks that ultimately contribute to the development and progression of AD are discussed. Finally, the drug candidates derived from herbs used as food or seasoning in Chinese daily life are summarized to provide a theoretical basis for improving the clinical treatment of AD.

Keywords: Alzheimer’s disease; calcium ions; mechanisms; review; transporters.