Paco Muñoz

Group website

Research Outline

Our work focuses on the study of the production, aggregation and neurotoxicity of amyloid ß-peptide (Aß) and its relationship with nitro-oxidative stress. Recently we have found that some natural peptides as the C-term of the human albumin inhibits Aβ aggregation and even induces the disassembling of Aβ fibrils protecting neurons. Moreover, we have demonstrated that oxidative stress and Aß oligomers induce BACE1 expression and Aß production by the phosphorylation of the eukaryotic translation initiation factor 2 alpha (eIF2alpha) generating a noxious loop of Aß damages and Aß production.

 

Research Lines

Title: 1 Study of the effect of calcium dysregulation in Alzheimer’s disease.

Description: We studied the implications of different proteins found in a yeast screening (in collaboration with other groups of the DCEXS) that protect against amyloid toxicity or that contribute directly to the toxic effect of Aß. These proteins have been selected by their ability to regulate calcium or to be activated by calcium. Their effects on intracellular calcium, amyloid production and toxicity are currently studied in our laboratory.

 

Title 2: Study of the interaction between Aß and insulin signalling in neurons.

Description: We are studying in collaboration with other groups of the DCEXS the role of Aß in the regulation of insulin intracellular signalling attending to AKT and GSK2beta phosphorylation and the consequences in the generation of insulin resistance and AD.

 

Team during 2019-20

PhD students: Pol Picón Pagès, Victor Herrera Fernández

 

Technicians: Cristina Plata Fernández

 

Selected publications 

- Picón-Pagès P, Gutiérrez DA, Barranco-Almohalla A, Crepin G, Tajes M, Ill-Raga G, Guix FX, Menéndez S, Arumí-Uría M, Vicente R, Álvarez AR, Muñoz FJ (2020). Amyloid beta-peptide increases BACE1 translation through the phosphorylation of the eukaryotic initiation factor-a. Oxidative Medicine and Cellular Longevity. 2020:  2739459. doi: 10.1155/2020/2739459. eCollection 2020.

 

- Picón-Pagès P, Bonet J, García-García J, Garcia-Buendia J, Gutierrez D, Valle J, Gómez-Casuso CES, Sidelkivska V, Alvarez A, Perálvarez-Marín A, Suades A, Fernàndez-Busquets X, Andreu D, Vicente R, Oliva B, Muñoz FJ (2019). Human albumin impairs amyloid ß-peptide fibrillation through its C-terminus: from docking modeling to protection against neurotoxicity in alzheimer's disease. Computational and Structural Biotechnology Journal. 17. p. 963 – 971. doi: 10.1016/j.csbj.2019.06.017. eCollection 2019.

 

- Picón-Pagès P, Garcia-Buendia J, Muñoz FJ (2019) Functions and dysfunctions of nitric oxide in brain.  Biochim Biophys Acta Mol Basis Dis 4439(18)30452-6. doi: 10.1016/j.bbadis.2018.11.007.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Amyloid1-40 beta fibrils showing the characteristic amyloid morphology (unbranched, twisted and constant diameter) analysed by Atomic Force Microscopy.