Cystamine and cysteamine increase brain levels of BDNF in Huntington disease via HSJ1b and transglutaminase

There is no treatment for the neurodegenerative disorder Huntington disease (HD). Cystamine is a candidate drug; however, the mechanisms by which it operates remain unclear. We show here that cystamine increases levels of the heat shock DnaJ-containing protein 1b (HSJ1b) that are low in HD patients. HSJ1b inhibits polyQ-huntingtin¿induced death of striatal neurons and neuronal dysfunction in Caenorhabditis elegans. This neuroprotective effect involves stimulation of the secretory pathway through formation of clathrin-coated vesicles containing brain-derived neurotrophic factor (BDNF). Cystamine increases BDNF secretion from the Golgi region that is blocked by reducing HSJ1b levels or by overexpressing transglutaminase. We demonstrate that cysteamine, the FDA-approved reduced form of cystamine, is neuroprotective in HD mice by increasing BDNF levels in brain. Finally, cysteamine increases serum levels of BDNF in mouse and primate models of HD. Therefore, cysteamine is a potential treatment for HD, and serum BDNF levels can be used as a biomarker for drug efficacy.

Conditional BDNF release under pathological conditions improves Huntington's disease pathology by delaying neuronal dysfunction

Background Brain-Derived Neurotrophic Factor (BDNF) is the main candidate for neuroprotective therapy for Huntington's disease (HD), but its conditional administration is one of its most challenging problems. Results Here we used transgenic mice that over-express BDNF under the control of the Glial Fibrillary Acidic Protein (GFAP) promoter (pGFAP-BDNF mice) to test whether up-regulation and release of BDNF, dependent on astrogliosis, could be protective in HD. Thus, we cross-mated pGFAP-BDNF mice with R6/2 mice to generate a double-mutant mouse with mutant huntingtin protein and with a conditional over-expression of BDNF, only under pathological conditions. In these R6/2:pGFAP-BDNF animals, the decrease in striatal BDNF levels induced by mutant huntingtin was prevented in comparison to R6/2 animals at 12 weeks of age. The recovery of the neurotrophin levels in R6/2:pGFAP-BDNF mice correlated with an improvement in several motor coordination tasks and with a significant delay in anxiety and clasping alterations. Therefore, we next examined a possible improvement in cortico-striatal connectivity in R62:pGFAP-BDNF mice. Interestingly, we found that the over-expression of BDNF prevented the decrease of cortico-striatal presynaptic (VGLUT1) and postsynaptic (PSD-95) markers in the R6/2:pGFAP-BDNF striatum. Electrophysiological studies also showed that basal synaptic transmission and synaptic fatigue both improved in R6/2:pGAP-BDNF mice. Conclusions These results indicate that the conditional administration of BDNF under the GFAP promoter could become a therapeutic strategy for HD due to its positive effects on synaptic plasticity.

Potencial de mercado y estructura espacial de los salarios en las regiones españolas, 1955-1995

En este artículo se examina la relación existente entre los salarios de las regiones españolas y su potencial de mercado en el período 1955-1995. Se prueba la existencia de una estructura espacial de los salarios, en la que los salarios disminuyen al alejarnos de las regiones de renta elevada. Este resultado refuerza la hipótesis de la existencia de una dinámica aglomerativa en España durante la segunda mitad del siglo XX. Sin embargo, el efecto del potencial de mercado sobre los salarios disminuye en la segunda parte del período (1975-1995). Este resultado es consistente con la apertura de una senda de dispersión en la localización de la actividad industrial a partir de mediados de los setenta

Foreign trade traps in the european periphery: Spain, 1870-1913

In this article we research into the difficulties that foreign trade imposed onSpanish process of integration into the international economy in the years priorto the First World War. We start out by examining some features of the foreigntrade structure of the country. By means of an econometric analysis of importand export series, it is possible to observe the presence of a trend towards tradedeficit, which was in force when Spain grew at a rate similar to that of itstrading partners. We also check that, in the absence of these compensatorymechanisms, adjustment in foreign payments could be reached by means ofprotective measures and the exchange rate.

Networks of people in specialty production: family firms in the iron and steel Wire industries in Spain (1870-2000)

Capital intensive industries in specialized niches of production have constituted solid ground for family firms in Spain , as evidenced by the experience of the iron and steel wire industries between 1870 and 2000. The embeddedness of these firms in their local and regional environments have allowed the creation of networks that, together with favourable institutional conditions, significantly explain the dominance of family entrepreneurship in iron and steel wire manufacturing in Spain, until the end of the 20 th century. Dominance of family firms at the regional level has not been not an obstacle for innovation in wire manufacturing in Spain, which has taken place even when institutional conditions blocked innovation and traditional networking. Therefore, economic theories about the difficulties dynastic family firms may have to perform appropriately in science-based industries must be questioned

Potencial de mercado y estructura espacial de los salarios en las regiones españolas, 1955-1995

En este artículo se examina la relación existente entre los salarios de las regiones españolas y su potencial de mercado en el período 1955-1995. Se prueba la existencia de una estructura espacial de los salarios, en la que los salarios disminuyen al alejarnos de las regiones de renta elevada. Este resultado refuerza la hipótesis de la existencia de una dinámica aglomerativa en España durante la segunda mitad del siglo XX. Sin embargo, el efecto del potencial de mercado sobre los salarios disminuye en la segunda parte del período (1975-1995). Este resultado es consistente con la apertura de una senda de dispersión en la localización de la actividad industrial a partir de mediados de los setenta

Foreign trade traps in the european periphery: Spain, 1870-1913

In this article we research into the difficulties that foreign trade imposed onSpanish process of integration into the international economy in the years priorto the First World War. We start out by examining some features of the foreigntrade structure of the country. By means of an econometric analysis of importand export series, it is possible to observe the presence of a trend towards tradedeficit, which was in force when Spain grew at a rate similar to that of itstrading partners. We also check that, in the absence of these compensatorymechanisms, adjustment in foreign payments could be reached by means ofprotective measures and the exchange rate.

Networks of people in specialty production: family firms in the iron and steel Wire industries in Spain (1870-2000)

Capital intensive industries in specialized niches of production have constituted solid ground for family firms in Spain , as evidenced by the experience of the iron and steel wire industries between 1870 and 2000. The embeddedness of these firms in their local and regional environments have allowed the creation of networks that, together with favourable institutional conditions, significantly explain the dominance of family entrepreneurship in iron and steel wire manufacturing in Spain, until the end of the 20 th century. Dominance of family firms at the regional level has not been not an obstacle for innovation in wire manufacturing in Spain, which has taken place even when institutional conditions blocked innovation and traditional networking. Therefore, economic theories about the difficulties dynastic family firms may have to perform appropriately in science-based industries must be questioned

Potencial de mercado y estructura espacial de los salarios en las regiones españolas, 1955-1995

En este artículo se examina la relación existente entre los salarios de las regiones españolas y su potencial de mercado en el período 1955-1995. Se prueba la existencia de una estructura espacial de los salarios, en la que los salarios disminuyen al alejarnos de las regiones de renta elevada. Este resultado refuerza la hipótesis de la existencia de una dinámica aglomerativa en España durante la segunda mitad del siglo XX. Sin embargo, el efecto del potencial de mercado sobre los salarios disminuye en la segunda parte del período (1975-1995). Este resultado es consistente con la apertura de una senda de dispersión en la localización de la actividad industrial a partir de mediados de los setenta

Potencial de mercado y estructura espacial de los salarios en las regiones españolas, 1955-1995

En este artículo se examina la relación existente entre los salarios de las regiones españolas y su potencial de mercado en el período 1955-1995. Se prueba la existencia de una estructura espacial de los salarios, en la que los salarios disminuyen al alejarnos de las regiones de renta elevada. Este resultado refuerza la hipótesis de la existencia de una dinámica aglomerativa en España durante la segunda mitad del siglo XX. Sin embargo, el efecto del potencial de mercado sobre los salarios disminuye en la segunda parte del período (1975-1995). Este resultado es consistente con la apertura de una senda de dispersión en la localización de la actividad industrial a partir de mediados de los setenta

Deporte y modernización en el ámbito mediterráneo. Reflexiones para una historia comparada (1870-1925)

The authors point out the main lines of the development of sportive practices on Mediterranean countries, during XX th century. They also expose some methodological issues as a contribute to the making of a social and cultural history of sports.

Deporte y modernización en el ámbito mediterráneo. Reflexiones para una historia comparada (1870-1925)

The authors point out the main lines of the development of sportive practices on Mediterranean countries, during XX th century. They also expose some methodological issues as a contribute to the making of a social and cultural history of sports.

Producció de valor, recursos humans i articulació de l'espai. Catalunya com a exemple (1955-1975)

Com a base per endinsar-se en l'anhlisi de l'articulació espacial d'un territori, proposo postular que aquesta articulació, és a dir, l'espai social en cada moment determinat, és la resultant dels efectes de la formació social vigent sobre una situació genealbgica del territori en el qual intervé. Segons aixb, la variable articuladora en cada formació social estarh formada pel procés de producció i reproducció de valor en la seqükncia: 1) producció de valor; 2) utilització dels diversos recursos productius, tot aprofitant-se de la mobilitat diferencial dels factors; 3) circulació del valor, i 4) gestió i/o apropiació de l'excedent i repartiment social del valor. Tot aixb sobre un territori en el qual s'articularan diverses funcionalitzacions de manera que possibilitin, i maximalitzin si és possible, el resultat per part del bloc gestor-apropiador de l'excedent.

Arquitectura, societat i construccíó de Gírona entre 1936 i 1955

Anàlisi de l'arquitectura de Girona entre l'any de l'aixecament militar del general Franco contra la República i elconsegüent inici de la Guerra Civil (1936) fins a l'any en què Espanya va ser admesa per ingressar a l'ONU (1955)

Memoria oral y alimentación: estrategias de supervivencia durante la Guerra Civil Española (1936-1939) y la posguerra (1939-1955)

El principal objetivo de nuestro tra bajo es delimitar las prácticas de reciprocidad que se llevaron a cabo durante el período de tiempo analizado y que permitieron reproducirse socialmente a los grupos menos favorecidos por la guerra y la posguerra . Nuestro análisis demuestra que la alimentación es un sistema de comuni - cación mediante el cual se crean o mantienen prácticas de poder , así como expre - siones de identidad y/o defensa o ruptura de las normas morales que comparte un grupo social .