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Titolo:
Hyperphosphorylated tan and neurofilament and cytoskeletal disruptions in mice overexpressing human p25, an activator of cdk5
Autore:
Ahlijanian, MK; Barrezueta, NX; Williams, RD; Jakowski, A; Kowsz, KP; McCarthy, S; Coskran, T; Carlo, A; Seymour, PA; Burkhardt, JE; Nelson, RB; McNeish, JD;
Indirizzi:
Pfizer Inc, Cent Res, Dept CNS Discovery, Groton, CT 06340 USA Pfizer IncGroton CT USA 06340 , Dept CNS Discovery, Groton, CT 06340 USA Pfizer Inc, Cent Res, Dept Genet Technol, Groton, CT 06340 USA Pfizer IncGroton CT USA 06340 , Dept Genet Technol, Groton, CT 06340 USA
Titolo Testata:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
fascicolo: 6, volume: 97, anno: 2000,
pagine: 2910 - 2915
SICI:
0027-8424(20000314)97:6<2910:HTANAC>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
CYCLIN-DEPENDENT KINASE-5; PAIRED HELICAL FILAMENTS; MICROTUBULE-BINDING; ALZHEIMERS-DISEASE; PROTEIN-KINASE; NEUROFIBRILLARY TANGLES; NERVOUS-SYSTEM; PHOSPHORYLATION; BRAIN; IMMUNOREACTIVITY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Ahlijanian, MK Pfizer Inc, Cent Res, Dept CNS Discovery, Eastern Point Rd,Groton, CT 06340 USA Pfizer Inc Eastern Point Rd Groton CT USA 06340 T 06340 USA
Citazione:
M.K. Ahlijanian et al., "Hyperphosphorylated tan and neurofilament and cytoskeletal disruptions in mice overexpressing human p25, an activator of cdk5", P NAS US, 97(6), 2000, pp. 2910-2915

Abstract

Hyperphosphorylation of microtubule-associated proteins such as tau and neurofilament may underlie the cytoskeletal abnormalities and neuronal death seen in several neurodegenerative diseases including Alzheimer's disease. One potential mechanism of microtubule-associated protein hyperphosphorylation is augmented activity of protein kinases known to associate with microtubules, such as cdk5 or GSK3 beta, Here we show that tau and neurofilament are hyperphosphorylated in transgenic mice that overexpress human p25, an activator of cdk5. The p25 transgenic mice display silver-positive neurons using the Bielschowsky stain. Disturbances in neuronal cytoskeletal organization are apparent at the ultrastructural level. These changes are localized predominantly to the amygdala, thalamus/hypothalamus, and cortex. The p25 transgenic mice display increased spontaneous locomotor activity and differences from control in the elevated plus-maze test. The overexpression of an activator of cdk5 in transgenic mice results in increased cdk5 activity that is sufficient to produce hyperphosphorylation of tau and neurofilament aswell as cytoskeletal disruptions reminiscent of Alzheimer's disease and other neurodegenerative diseases.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/11/20 alle ore 15:57:08