Cód. SSPA: IBiS-B-04
Alzheimer's, aging, neuroinflammation, reticulum stress
Alzheimer's disease (AD), a progressive neurodegenerative disease that predominantly affects people aged 65 and over, is the leading cause of dementia in the world. However, to date there is no effective pharmacological treatment against this disease. The absence of effective therapies is mainly due to the absence of good animal models and molecular markers of this pathology. Our main objective is the characterization, at the cellular and molecular level, of transgenic animal models of AD. Specifically, we are currently characterizing the possible involvement of the glial response (astro- and microglia), induced by the production of Abeta, in the mechanisms of neuronal protection and/or degeneration.
Results obtained by our group show that, in the tg PS1xAPP models, the degeneration of the main neurons occurs at late ages (12 to 18 months of age). However, the accumulation of Abeta is relatively early (3-4 months of age). Consequently, we are currently investigating the molecular mechanisms that determine this late neuronal death and the early neuroprotective mechanisms.
Another of our objectives is to characterize, at the molecular level, the modifications due to aging that occur in the response to cellular stress, caused by the accumulation of proteins (UPR and UPS systems), as well as the neuroinflammatory response associated with aging (factors involved in the origin and/or progression of Alzheimer's disease). Our idea is based on the premise that knowledge of the causes of neuroinflammatory processes and the accumulation of proteins during normal aging will provide us with information on how these two processes can trigger a pathological situation and therefore be able to treat it.
We are currently characterizing several transgenic models of Alzheimer's disease. Specifically, we are determining the neuropathological changes that these models undergo, as well as the causes that determine the aforementioned changes or deficiencies. On the other hand, we also investigated the deficiencies in the mechanisms of response to stress produced by the intracellular accumulation of proteins and their modifications with the age of the animal.
