Research Interest

Dr. Alberch’s group is interested in identifying new therapeutic targets to develop new treatments for Huntington’s disease.
Mutated huntingtin activates a series of intracellular mechanisms that produce selective degeneration of the striated nucleus projection neurons, initially the indirect pathway and later the direct route. This neuronal degeneration causes alterations in the basal ganglia circuits that is responsible for disease symptomatology: motor disorder and cognitive disorders. In recent years, our research group has described different mechanisms involved in degeneration induced by mutant huntingtin, such as the characterization of neurotrophic factors in this process, especially the BDNF. Currently, the main objective of the group is:  To study the molecular and cellular mechanisms activated by mutant huntingtin that alter the neuronal plasticity involved in the maintenance of the basal ganglia circuits affected by Huntington’s disease.

Cellular and molecular basis of Huntington’s disease and other disorders of the basal ganglia belongs to Creatio, Production and validation center for advanced therapies. (http://www.ub.edu/creatio)

Current Research Line

• Implication of the BDNF / TrkB / p75 system in the mechanisms of neuronal plasticity in Huntington’s disease.
• Control of the excitatory / inhibitor balance of the cortical and striatal neuronal networks and their involvement in the neurodegenerative processes.
• Optogenetic study to assess the involvement of the direct and indirect pathway in the basal ganglia in motor coordination altered in Huntington’s disease.
• Identification of new drugs that recover functional connectivity (glutamate-dopamine-acetylcholine-gaba) from neuronal circuits to basal ganglia.

Technologies/Methods

The different methods used by scientists are: stem cell culture and differentiation, co-culture of differentiated stem cells on multi-chamber/chip system, in vivo and in vitro optogenetics and optopharmacology, mouse behavioural analysis, in vivo neuron grafting, laser capture, high-throughput gene expression analysis, immunostainings and in situ hybridization, matrix microprinting, confocal and electronic microscopy, high-throughput content analysis, calcium imaging, branching and dendritic network analysis.

Hightlighted Publications

Pyk2 modulates hippocampal excitatory synapses and contributes to cognitive deficits in a Huntington’s disease model. Giralt A, Brito V, Chevy Q, Simonnet C, Otsu Y, Cifuentes-Díaz C, de Pins B, Coura R, Alberch J, Ginés S, Poncer JC, Girault JA. Nat Commun. 2017; 8:15592.

7,8 Dihydroxyflavone ameliorates cognitive and motor deficits in a Huntington’s disease mouse model through specific activation of the PLCγ1 pathway. García-Díaz Barriga G, Giralt A, Anglada-Huguet M, Gaja-Capdevila N, Orlandi JG, Soriano J, Canals JM, Alberch J. Hum Mol Genet. 2017 May 24.

Prostaglandin E2 EP2 activation reduces memory decline in R6/1 mouse model of Huntington’s disease by the induction of BDNF-dependent synaptic plasticity.

Anglada-Huguet M, Vidal-Sancho L, Giralt A, García-Díaz Barriga G, Xifró X, Alberch J.

Neurobiol Dis. 2016; 95:22-34.

Aberrant epigenome in iPSC-derived dopaminergic neurons from Parkinson’s disease patients. Fernández-Santiago R, Carballo-Carbajal I, Castellano G, Torrent R, Richaud Y, Sánchez-Danés A, Vilarrasa-Blasi R, Sánchez-Pla A, Mosquera JL, Soriano J, López-Barneo J, Canals JM, Alberch J, Raya Á, Vila M, Consiglio A, Martín-Subero JI, Ezquerra M, Tolosa E. EMBO Mol Med. 2015; 7(12):1529-46.

Fingolimod (FTY720) enhances hippocampal synaptic plasticity and memory in Huntington’s disease by preventing p75NTR up-regulation and astrocyte-mediated inflammation. Miguez A, García-Díaz Barriga G, Brito V, Straccia M, Giralt A, Ginés S, Canals JM, Alberch J. Hum Mol Genet. 2015 Sep 1;24(17):4958-70.