title: Alzheimer's disease: an update of the roles of receptors, astrocytes and primary cilia (review).
abstract: The pathophysiological mechanisms underlying the onset and inexorable progression             of the late‑onset form of Alzheimer's disease (AD) are still the object of controversy.             This review takes stock of some most recent advancements of this field concerning             the complex roles played by the amyloid‑β (Aβ)‑binding p75 neurotrophin receptor             (p75NTR) and calcium‑sensing receptor (CaSR) and by the primary cilia in AD. Apart             from their physiological roles, p75NTR is more intensely expressed in the hippocampus             of human AD brains and Aβ‑bound p75NTR triggers cell death, whereas Aβ‑bound CaSR             signalling induces the de novo synthesis and release of nitric oxide (NO), vascular             endothelial growth factor (VEGF)‑A and Aβ peptides (Aβs), particularly on the             part of normal adult human astrocytes. The latter effect could significantly increase             the pool of Aβ‑ and NO‑producing nerve cells favouring the progressive spread             of a self‑sustaining and self‑reinforcing 'infectious' mechanism of neural and             vascular (i.e. blood-brain barrier) cell damage. Interestingly, primary cilia             concentrate p75NTR receptors in their membranes and are abnormally structured/damaged             in transgenic (Tg) AD‑model mice, which could impact on the adult neurogenesis             occurring in the dentate gyrus's subgranular zone (SGZ) that is necessary for             new memory encoding, thereby favouring typical AD cognitive decline. Altogether,             these findings may pave the way to novel therapeutic approaches to AD, particularly             in its mild cognitive impairment (MCI) and pre‑MCI stages of development.
authors.affiliation: Histology and Embryology Section, Department of Life and Reproduction Sciences, University of Verona Medical School, Verona, Venetia, Italy. uarmato@hotmail.com
authors.forename: Ubaldo
authors.initials: U
authors.lastname: Armato
authors.forename: Balu
authors.initials: B
authors.lastname: Chakravarthy
authors.forename: Raffaella
authors.initials: R
authors.lastname: Pacchiana
authors.forename: James F
authors.initials: JF
authors.lastname: Whitfield
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D016923:Cell Death; D002923:Cilia / Q000378:metabolism*; D018891:Dentate Gyrus / Q000503:physiopathology; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism*; D044169:Receptors, Calcium-Sensing / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D016229:Amyloid beta-Peptides; D020800:Receptor, Nerve Growth Factor; D044169:Receptors, Calcium-Sensing