Novel multipotent AChEI-CCB attenuates hyperhomocysteinemia-induced memory deficits and Neuropathologies in rats.
J Alzheimers Dis
; 42(3): 1029-39, 2014.
Article
em En
| MEDLINE
| ID: mdl-25024319
ABSTRACT
Alzheimer's disease (AD) has multiple etiopathogenic factors, yet the definitive cause remains unclear and the therapeutic strategies have been elusive. Combination therapy, as one of the promising treatments, has been studied for years and may exert synergistic beneficial effects on AD through polytherapeutic targets. In this study, we tested the effects of a synthesized juxtaposition (named SCR1693) composed of an acetylcholinesterase inhibitor (AChEI) and a calcium channel blocker (CCB) on the hyperhomocysteinemia (HHcy)-induced AD rat model, and found that SCR1693 remarkably improved the HHcy-induced memory deficits and preserved dendrite morphologies as well as spine density by upregulating synapse-associated proteins PSD95 and synapsin-1. In addition, SCR1693 attenuated HHcy-induced tau hyperphosphorylation at multiple AD-associated sites by regulating the activity of protein phosphatase-2A and glycogen synthase kinase-3ß. Furthermore, SCR1693 was more effective than individual administration of both donepezil and nilvadipine which were used as AChEI and CCB, respectively, in the clinical practice. In conclusion, our data suggest that the polytherapeutic targeting juxtaposition SCR1693 (AChEI-CCB) is a promising therapeutic candidate for AD.
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Texto completo:
1
Base de dados:
MEDLINE
Métodos Terapêuticos e Terapias MTCI:
Terapias_biologicas
/
Aromoterapia
Assunto principal:
Encefalopatias
/
Bloqueadores dos Canais de Cálcio
/
Inibidores da Colinesterase
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Hiper-Homocisteinemia
/
Transtornos da Memória
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Idioma:
En
Revista:
J Alzheimers Dis
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
China