Astroglial calcium signalling in Alzheimer's disease

Abstract

Neuroglial contribution to Alzheimer's disease (AD) is pathologically relevant and highly heterogeneous. Reactive astrogliosis and activation of microglia contribute to neuroinflammation, whereas astroglial and oligodendroglial atrophy affect synaptic transmission and underlie the overall disruption of the central nervous system (CNS) connectome. Astroglial function is tightly integrated with the intracellular ionic signalling mediated by complex dynamics of cytosolic concentrations of free Ca²⁺ and Na⁺. Astroglial ionic signalling is mediated by plasmalemmal ion channels, mainly associated with ionotropic receptors, pumps and solute carrier transporters, and by intracellular organelles comprised of the endoplasmic reticulum and mitochondria. The relative contribution of these molecular cascades/organelles can be plastically remodelled in development and under environmental stress. In AD astroglial Ca²⁺ signalling undergoes substantial reorganisation due to an abnormal regulation of expression of Ca²⁺ handling molecular cascades.

Keywords: Alzheimer's disease; Astrocyte; Astroglial atrophy; Astrogliosis; Calcium signalling; Glutamate receptors; InsP(3) receptors; Neuroglia; β-amyloid.