Alzheimer's disease: An update of the roles of receptors, astrocytes and primary cilia (Review)

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Journal titleInternational Journal of Molecular Medicine
Pages310; # of pages: 8
Subjectamyloid beta protein; amyloid beta-peptides; calcium sensing receptor; glial fibrillary acidic protein; guanosine triphosphate cyclohydrolase I; inducible nitric oxide synthase; neurotrophin receptor p75; protein Patched; protein tyrosine kinase A; smoothened protein; somatomedin C receptor; sonic hedgehog protein; tetrahydrobiopterin; vasculotropin A; cell damage; ciliary body; dentate gyrus; enzyme activity; granule cell; intracellular signaling; mild cognitive impairment; nerve cell necrosis; nerve cell primary cilia; neural stem cell; neuroblastoma cell; protein expression; protein phosphorylation; signal transduction; cell Death; dentate gyrus; hippocampus; neurogenesis; neurons; receptor, nerve growth factor; receptors, calcium-sensing; signal transduction
AbstractThe 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.
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AffiliationHuman Health Therapeutics; National Research Council Canada
Peer reviewedYes
NPARC number21270456
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Record identifierdc261f57-494a-4c4b-a290-9647232dd286
Record created2014-02-12
Record modified2016-05-09
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