A - Human Necessities – 61 – K
Patent
A - Human Necessities
61
K
A61K 31/192 (2006.01) A61P 25/28 (2006.01)
Patent
CA 2718463
The use of 4PBA in the manufacture of a medicament useful to treat cognitive disorders in dementias coursing with tauopathies is described. The treatment with 4PBA improves cognitive deficit in a classic murine experimental model of Alzheimer's Disease (AD) (Tg 2576) that is accompanied by decreasing levels of a marker characteristic to AD pathologies, such as phosphorylated Tau, and increasing levels in the synthesis of some synaptic plasticity marker proteins such as GluR1 and PSD95. As mediating mechanism for the therapeutic effect we propose a decreasing stress in the endoplasmic reticulum as manifested by increasing levels of the GRP78 protein. On the other hand its inhibiting effect on histone deacetylation and its involvement in chromatin remodeling facilitates protein synthesis processes, which improves synaptic plasticity.
Se describe el uso del 4-fenilbutirato de sodio (4 PBA) en la fabricación de un medicamento útil para el tratamiento de trastornos cognitivos en demencias que cursan con taupatías. El tratamiento con 4 PBA mejora el déficit cognitivo de un modelo murino clásico de Enfermedad de Alzheimer (EA) (Tg 2576), que se acompaña con la disminución de un marcador característico de patología EA, como es la Tau fosforilada, y en el incremento de la síntesis de algunas proteínas marcadoras de la plasticidad sináptica, como GIuR1 y PSD95. Como mecanismo mediador del efecto terapéutico proponemos la disminución del estrés en el retículo endoplásmico manifestada en forma de incremento de la proteína GRP78. Por otro lado su efecto como inhibidor de la desacetilación de histonas y su implicación en la remodelización de la cromatina facilita los procesos de síntesis proteica, lo que mejora la plasticidad sináptica.
Frechilla Manso Diana Sara
Garcia Osta Ana Maria
Perez Mediavilla Luis Alberto
Ricobaraza Abarquero Ana Lourdes
Marks & Clerk
Proyecto de Biomedicina Cima S.l.
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