Alternative Targets to Fight Alzheimer’s Disease: Focus on Astrocytes

Abstract

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.

Cholesterol Dysmetabolism in Alzheimer’s Disease: A Starring Role for Astrocytes?

“…Impaired cholesterol metabolism and astrocyte reactivity in the brain are key factors in AD onset and progression. Indeed, the idea that targeting astrocytes [ 199 , 200 , 201 ] or maintaining cholesterol homeostasis [ 152 , 198 ] could represent new potential therapeutic strategies to inhibit or delay AD progression is gaining ground. However, understanding of their mutual influence needs to be further developed, in particular whether and how brain cholesterol dysmetabolism affects astrocyte reactivity and vice versa.…”

Microglia and astrocyte involvement in neurodegeneration and brain cancer

“…4 ). Special interest has been paid to the dysfunction of cellular metabolism and bioenergetic fitness as a possible genesis of neuropathology, for example the neuroenergetic hypothesis of AD or the Warburg and reverse Warburg hypotheses in cancer [ 98 , 105 ]. Several different molecular glial targets can be modulated by gene therapy, recombinant proteins, epigenetic, transcription and translation regulators or nonsense suppression.…”

Successful and Unsuccessful Brain Aging in Pets: Pathophysiological Mechanisms behind Clinical Signs and Potential Benefits from Palmitoylethanolamide Nutritional Intervention

“…Interestingly, PEA is able to modulate the activity of both glial and mast cells, thus representing a very promising therapeutic tool to treat neurological disorders [ 217 ]. Several studies have indeed highlighted the ability of PEA to modulate the reactivity of these cells, mainly limiting the release of pro-inflammatory and neurotoxic mediators and favoring neuronal survival [ 180 , 181 , 218 , 219 , 220 ].…”