Browsing by Author "Von Bernhardi Montgomery, Rommy Edth B."
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- Itemc-Abl tyrosine kinase modulates tau pathology and Cdk5 phosphorylation in AD transgenic mice(2011) Cancino Lobos, Gonzalo; Pérez De Arce Guzmán, Karen Andrea; Castro Uribe, Paula Andrea; Toledo Maldonado, Enrique Daniel; Von Bernhardi Montgomery, Rommy Edth B.; Álvarez Rojas, Alejandra BeatrizThe c-Abl tyrosine kinase is an important link in signal transduction pathways that promote cytoskeletal rearrangement and apoptotic signalling. We have previously shown that amyloid-beta-peptide (A beta) activates c-Abl. Herein we show that c-Abl participates in A beta-induced tau phosphorylation through Cdk5 activation. We found that intraperitoneal administration of STI571, a specific inhibitor for c-Abl kinase, decreased tau phosphorylation in the APPswe/PSEN1 Delta E9 transgenic mouse brain. In addition, when neurons were treated with A beta we observed: (i) an increase in active c-Abl and tau phosphorylation, (ii) the prevention of tau phosphorylation by STI571 and (iii) the inhibition of c-Abl expression by shRNA, as well as the expression of a c-Abl kinase death mutant, decreased AT8 and PHF1 signals. Furthermore, the increase of c-Abl was associated with Tyr15 phosphorylation of Cdk5 and its association with c-Abl. Brains from APPswe/PSEN1 Delta E9 mice showed higher levels of c-Abl and phospho-Cdk5 than wild-type mice. Moreover, STI571 treatment decreased the phospho-Cdk5 levels. Together, the evidence suggests that activation of c-Abl by A beta promotes tau phosphorylation through Tyr15 phosphorylation-mediated Cdk5 activation. (C) 2009 Elsevier Inc. All rights reserved.
- ItemEl síndrome metabólico: de factor agravante a principal factor de riesgo patogénico en diversas enfermedades crónicas(2010) Von Bernhardi Montgomery, Rommy Edth B.; Zanlungo Matsuhiro, Silvana; Arrese Jiménez, Marco Antonio; Arteaga Llona, Antonio Alberto; Rigotti Rivera, Attilio GianpietroIn recent years, a rapidly increasing number of studies have focused on the association between metabolic syndrome and several chronic diseases. However, it is difficult to determine a well defined pathogenic relationship, due to the etiological heterogeneity and comorbidities of these diseases. Research efforts are aiming to identify the convergent biological mechanisms that mediate the effects of hyperinsulinemia, hyperglycemia, dyslipidemia, and hypertension. All these conditions define the metabolic syndrome, that increases the risk for several diseases. The knowledge of these biological mechanisms associated with this syndrome will elucidate the pathogenic association between a variety of chronic diseases, including its pathogenic link with cardiovascular diseases and the most common forms of dementia. The development of new therapeutic and preventive strategies for these diseases will be a corollary of this research.
- ItemMicroglia Function in the Normal Brain(2016) Heredia, María Florencia; Muñoz Reyes, Paola Cecilia; Salgado Cortés, Nicole Andrea; Von Bernhardi Montgomery, Rommy Edth B.The activation of microglia has been recognized for over a century by their morphological changes. Long slender microglia acquire a short sturdy ramified shape when activated. During the past 20 years, microglia have been accepted as an essential cellular component for understanding the pathogenic mechanism of many brain diseases, including neurodegenerative diseases. More recently, functional studies and imaging in mouse models indicate that microglia are active in the healthy central nervous system. It has become evident that microglia release several signal molecules that play key roles in the crosstalk among brain cells, i.e., astrocytes and oligodendrocytes with neurons, as well as with regulatory immune cells. Recent studies also reveal the heterogeneous nature of microglia diverse functions depending on development, previous exposure to stimulation events, brain region of residence, or pathological state. Subjects to approach by future research are still the unresolved questions regarding the conditions and mechanisms that render microglia protective, capable of preventing or reducing damage, or deleterious, capable of inducing or facilitating the progression of neuropathological diseases. This novel knowledge will certainly change our view on microglia as therapeutic target, shifting our goal from their general silencing to the generation of treatments able to change their activation pattern.