title: Glial calcium signalling in Alzheimer's disease.
abstract: The most accredited (and fashionable) hypothesis of the pathogenesis of Alzheimer Disease (AD) sees accumulation of β-amyloid protein in the brain (in both soluble and insoluble forms) as a leading mechanism of neurotoxicity. How β-amyloid triggers the neurodegenerative disorder is at present unclear, but growing evidence suggests that a deregulation of Ca(2+) homeostasis and deficient Ca(2+) signalling may represent a fundamental pathogenic factor. Given that symptoms of AD are most likely linked to synaptic dysfunction (at the early stages) followed by neuronal loss (at later and terminal phases of the disease), the effects of β-amyloid have been mainly studied in neurones. Yet, it must be acknowledged that neuroglial cells, including astrocytes, contribute to pathological progression of most (if not all) neurological diseases. Here, we review the literature pertaining to changes in Ca(2+) signalling in astrocytes exposed to exogenous β-amyloid or in astrocytes from transgenic Alzheimer disease animals models, characterized by endogenous β-amyloidosis. Accumulated experimental data indicate deregulation of Ca(2+) homeostasis and signalling in astrocytes in AD, which should be given full pathogenetic consideration. Further studies are warranted to comprehend the role of deficient astroglial Ca(2+) signalling in the disease progression.
authors.affiliation: Department of Pharmaceutical Sciences, Università del Piemonte Orientale, Via Bovio 6, 28100, Novara, Italy.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Lim
authors.forename: Virginia
authors.initials: V
authors.lastname: Ronco
authors.forename: Ambra A
authors.initials: AA
authors.lastname: Grolla
authors.forename: Alexei
authors.initials: A
authors.lastname: Verkhratsky
authors.forename: Armando A
authors.initials: AA
authors.lastname: Genazzani
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000502:physiology; D000818:Animals; D020013:Calcium Signaling; D006801:Humans; D009457:Neuroglia / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides