title: β-adrenergic receptors and G protein-coupled receptor kinase-2 in Alzheimer's disease: a new paradigm for prognosis and therapy?
abstract: Alzheimer's disease (AD) is a devastating form of dementia that imposes a severe burden on health systems and society. Although several aspects of AD pathogenesis have been elucidated over the last few decades, many questions still need to be addressed. In fact, currently available medications only provide symptomatic improvement in patients with AD without affecting disease progression. The β-adrenergic receptor (β-AR) system can be considered a possible target that deserves further exploration in AD. The central noradrenergic system undergoes substantial changes in the course of AD and β-ARs have been implicated not only in amyloid formation in AD brain but also in amyloid-induced neurotoxicity. Moreover, clinical evidence suggests a protective role of β-AR blockers on AD onset. In addition to that, post-receptor components of β-AR signaling seem to have a role in AD pathogenesis. In particular, the G protein coupled receptor kinase 2, responsible for β-AR desensitization and downregulation, mediates amyloid-induced β-AR dysfunction in neurons, and its levels in circulating lymphocytes of AD patients are increased and inversely correlated with patient's cognitive status. Therefore, there is an urgent need to gain further insight on the role of the adrenergic system components in AD pathogenesis in order to translate preclinical and clinical knowledge to more efficacious prognostic and therapeutic strategies.
authors.affiliation: Department of Medical Translational Sciences, Federico II University of Naples, Naples, Italy.
authors.forename: Grazia Daniela
authors.initials: GD
authors.lastname: Femminella
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rengo
authors.forename: Gennaro
authors.initials: G
authors.lastname: Pagano
authors.forename: Claudio
authors.initials: C
authors.lastname: de Lucia
authors.forename: Klara
authors.initials: K
authors.lastname: Komici
authors.forename: Valentina
authors.initials: V
authors.lastname: Parisi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cannavo
authors.forename: Daniela
authors.initials: D
authors.lastname: Liccardo
authors.forename: Carlo
authors.initials: C
authors.lastname: Vigorito
authors.forename: Pasquale Perrone
authors.initials: PP
authors.lastname: Filardi
authors.forename: Nicola
authors.initials: N
authors.lastname: Ferrara
authors.forename: Dario
authors.initials: D
authors.lastname: Leosco
mesh_terms: D018663:Adrenergic Agents / Q000008:administration & dosage / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D016503:Drug Delivery Systems / Q000639:trends; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000502:physiology*; D006801:Humans; D011379:Prognosis; D011485:Protein Binding / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
chemical_list: D018663:Adrenergic Agents; D011943:Receptors, Adrenergic, beta; D054769:G-Protein-Coupled Receptor Kinase 2