title: Pin1: a therapeutic target in Alzheimer neurodegeneration.
abstract: In Alzheimer's disease, the peptidyl prolyl cis/trans isomerase Pin1 binds to phospho-Thr231 on Tau proteins and, hence, is found within degenerating neurons, where it is associated to the large amounts of abnormally phosphorylated Tau proteins. Conversely, Pin1 may restore the tubulin polymerization function of these hyperphosphorylated Tau. In the present work, we investigated, both at the cellular and molecular levels, the role of Pin1 in Alzheimer's disease through the study of its interactions with phosphorylated Tau proteins. We also showed that in neuronal cells, Pin1 upregulates the expression of cyclin D1. This, in turn, could facilitate the transition from quiescence to the G1 phase (re-entry in cell cycle) in a neuron and, subsequently, neuronal dedifferentiation and apoptosis. The involvement of Pin1 in the G0/G1 transition in neurons points to its function as a good target for the development of new therapeutic strategies in neurodegenerative disorders.
authors.affiliation: INSERM U422, IMPRT, Place de Verdun, Lille, France.
authors.forename: Malika
authors.initials: M
authors.lastname: Hamdane
authors.forename: Caroline
authors.initials: C
authors.lastname: Smet
authors.forename: Anne-Véronique
authors.initials: AV
authors.lastname: Sambo
authors.forename: Arnaud
authors.initials: A
authors.lastname: Leroy
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Wieruszeski
authors.forename: Patrice
authors.initials: P
authors.lastname: Delobel
authors.forename: Claude-Alain
authors.initials: CA
authors.lastname: Maurage
authors.forename: Antoine
authors.initials: A
authors.lastname: Ghestem
authors.forename: René
authors.initials: R
authors.lastname: Wintjens
authors.forename: Séverine
authors.initials: S
authors.lastname: Bégard
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sergeant
authors.forename: André
authors.initials: A
authors.lastname: Delacourte
authors.forename: Dragos
authors.initials: D
authors.lastname: Horvath
authors.forename: Isabelle
authors.initials: I
authors.lastname: Landrieu
authors.forename: Guy
authors.initials: G
authors.lastname: Lippens
authors.forename: Luc
authors.initials: L
authors.lastname: Buée
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism*; D002460:Cell Line; D019938:Cyclin D1 / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009285:Naphthoquinones / Q000494:pharmacology; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000201:enzymology* / Q000473:pathology; D019696:Peptidylprolyl Isomerase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D013050:Spectrometry, Fluorescence; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009285:Naphthoquinones; D016875:tau Proteins; D019938:Cyclin D1; D010751:Phosphopyruvate Hydratase; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase; C005134:juglone