RESUMEN
Much evidence indicates that the memory and cognitive deficits of patients with Alzheimer's disease are closely associated with dysfunction of central cholinergic system. The degree of reduction of choline acetyltransferase activity in cerebral cholinergic neurons is significantly correlated with the severity of dementia or cognitive impairments observed in Alzheimer's disease. Therefore, Alzheimer's disease may be slowed by supplementation of exogenous choline acetyltransferase. Here we show that choline acetyltransferase mediated by TAT protein transduction domain passes through the blood-brain barrier and enters the neurons in mice, increasing choline acetyltransferase and neurotransmitter acetylcholine contents. The recombination TAT-choline acetyltransferase fusion protein injected intravenously improves the memory and cognitive dysfunction in Alzheimer's disease model mice induced by amyloid-beta peptide. Our results imply a novel and potentially effective way for Alzheimer's disease therapy.
Asunto(s)
Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/enzimología , Colina O-Acetiltransferasa/administración & dosificación , Terapias Complementarias/métodos , Modelos Animales de Enfermedad , Animales , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/enzimología , Colina O-Acetiltransferasa/biosíntesis , Relación Dosis-Respuesta a Droga , Hipocampo/efectos de los fármacos , Hipocampo/enzimología , Humanos , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/fisiología , RatonesRESUMEN
The so called "enzymatic preparations" Rheumajecta and Vasolastine (R & V) belong to the complementary treatments. The preparations have been used for many years in the treatment of patients with rheumatic conditions such as rheumatoid arthritis (RA) in the Netherlands and other countries of Europe, although a proper study showing efficacy was never performed. Therefore a double-blind, placebo-controlled, modified cross-over trial during two periods of 3 months was performed in 34 patients with RA. They were allocated at random to R & V or to placebo injections, all intramuscular. After 3 months of therapy each patient could opt for cross-over in the event of lack of subjective improvement. Clinical assessments including Ritchie's articular index, grip strength, the DUTCH-AIMS questionnaire, ESR and CRP were performed. R & V did not prove to be more effective than placebo. No serious side-effects were seen.