PubMed | University of Rome La Sapienza, University of Naples Naples and University Of Rome rconi Rome
Type: | Journal: Frontiers in neuroscience | Year: 2015
Data from animal models and Alzheimers disease (AD) subjects provide clear evidence for an activation of inflammatory pathways during the pathogenetic course of such illness. Biochemical and neuropathological studies highlighted an important cause/effect relationship between inflammation and AD progression, revealing a wide range of genetic, cellular, and molecular changes associated with the pathology. In this context, glial cells have been proved to exert a crucial role. These cells, in fact, undergo important morphological and functional changes and are now considered to be involved in the onset and progression of AD. In particular, astrocytes respond quickly to pathology with changes that have been increasingly recognized as a continuum, with potentially beneficial and/or negative consequences. Although it is now clear that activated astrocytes trigger the neuroinflammatory process, however, the precise mechanisms have not been completely elucidated. Neuroinflammation is certainly a multi-faceted and complex phenomenon and, especially in the early stages, exerts a reparative intent. However, for reasons not yet all well known, this process goes beyond the physiologic control and contributes to the exacerbation of the damage. Here we scrutinize some evidence supporting the role of astrocytes in the neuroinflammatory process and the possibility that these cells could be considered a promising target for future AD therapies.
Steardo L.,University of Naples Naples |
Signorile A.,University of Bari |
Scuderi C.,University of Rome La Sapienza |
Carratu M.R.,University of Bari
Drugs of the Future | Year: 2016
Retinoids are a class of natural and synthetic molecules structurally and/or functionally related to all-trans-retinoic acid (ATRA), a metabolite of Vitamin A (retinol). The retinoid system controls the expression of hundreds of genes, including transcription factors, enzymes, structural proteins, cell surface receptors, neurotransmitters, hormones and growth factors, hence modulating cell proliferation, differentiation, morphogenesis and immunity. The retinoid-associated signaling plays a critical role in neurodevelopment and remains active in the adult central nervous system, thus assuming high relevance in the context of neurodegeneration. The ability of retinoids to exert antioxidant effects, decrease β-amyloid (Aβ) accumulation, improve neurotransmission, suppress neuroinflammation and promote neural regeneration is discussed. Although retinoids with their pleiotropic activity are revealing a promising approach for the management of Alzheimer's disease (AD), timing as well as appropriate dosage and safety still remain a challenge. In particular, assuming that the end-stage lesions (senile plaques and neurofibrillary tangles) are an adaptive response to oxidative stress underlying AD, late administration of retinoids could paradoxically suppress a protective mechanism by inhibiting Aβ deposits. © 2016 Prous Science, S.A.U. or its licensors. All rights reserved.