RESUMO
The available treatments for patients affected by Alzheimer's disease (AD) are not curative. Numerous clinical trials have failed during the past decades. Therefore, scientists need to explore new avenues to tackle this disease. In the present review, we briefly summarize the pathological mechanisms of AD known so far, based on which different therapeutic tools have been designed. Then, we focus on a specific approach that is targeting astrocytes. Indeed, these non-neuronal brain cells respond to any insult, injury, or disease of the brain, including AD. The study of astrocytes is complicated by the fact that they exert a plethora of homeostatic functions, and their disease-induced changes could be context-, time-, and disease specific. However, this complex but fervent area of research has produced a large amount of data targeting different astrocytic functions using pharmacological approaches. Here, we review the most recent literature findings that have been published in the last five years to stimulate new hypotheses and ideas to work on, highlighting the peculiar ability of palmitoylethanolamide to modulate astrocytes according to their morpho-functional state, which ultimately suggests a possible potential disease-modifying therapeutic approach for AD.
Assuntos
Doença de Alzheimer/metabolismo , Astrócitos/metabolismo , Gliose/metabolismo , Fármacos Neuroprotetores/farmacologia , Doença de Alzheimer/complicações , Doença de Alzheimer/tratamento farmacológico , Animais , Astrócitos/efeitos dos fármacos , Gliose/tratamento farmacológico , Gliose/etiologia , Humanos , Fármacos Neuroprotetores/uso terapêuticoRESUMO
BACKGROUND: At the earliest stage of Alzheimer's disease (AD), although patients are still asymptomatic, cerebral alterations have already been triggered. In addition to beta amyloid (Aß) accumulation, both glial alterations and neuroinflammation have been documented at this stage. Starting treatment at this prodromal AD stage could be a valuable therapeutic strategy. AD requires long-term care; therefore, only compounds with a high safety profile can be used, such as the new formulation containing palmitoylethanolamide and luteolin (co-ultra PEALut) already approved for human use. Therefore, we investigated it in an in vivo pharmacological study that focused on the prodromal stage of AD. METHODS: We tested the anti-inflammatory and neuroprotective effects of co-ultra PEALut (5 mg/Kg) administered for 14 days in rats that received once, 5 µg Aß(1-42) into the hippocampus. RESULTS: Glial activation and elevated levels of proinflammatory mediators were observed in Aß-infused rats. Early administration of co-ultra PEALut prevented the Aß-induced astrogliosis and microgliosis, the upregulation in gene expression of pro-inflammatory cytokines and enzymes, as well as the reduction of mRNA levels BDNF and GDNF. Our findings also highlight an important neuroprotective effect of co-ultra PEALut treatment, which promoted neuronal survival. CONCLUSIONS: Our results reveal the presence of cellular and molecular modifications in the prodromal stage of AD. Moreover, the data presented here demonstrate the ability of co-ultra PEALut to normalize such Aß-induced alterations, suggesting it as a valuable therapeutic strategy.