Neuroinflammation in Alzheimer’s Disease: Friend or Foe?

Neuroinflammation is part of the complex immune response within the central nervous system (CNS), whose details have been partially elucidated. The CNS immune response involves elements carried from the periphery and resident elements, mainly represented by glial cells. These cells drive neuroinflammation, which can be roughly defined as an articulated physiological response characterized by the production of a plethora of inflammatory mediators that alter the microenvironment.

Growing evidence shows roles for neuroinflammation in the aging brain both in healthy and pathological conditions, including Alzheimer’s disease (AD). AD is a multifactorial neurodegenerative disease of the brain, characterized, at the molecular level, by deposits of beta‐amyloid peptides in the extracellular space and of neurofibrillary tangles inside neurons. Together with abnormal protein deposits, it is now established that neuroinflammation represents the third hallmark found in AD patients’ brains. Many scientists agree that the neuroinflammatory process begins at the earliest phase of AD, bringing both positive and negative consequences.

Indeed, the brain immune system recognizes the abnormal accumulation of proteins as injurious stimuli, so it initiates a physiological reaction to defend the brain that includes activation of glial cells and release of proinflammatory molecules. When these processes are protracted, they may contribute independently to neural dysfunction, cell death, thus fostering AD progression. Based on these considerations, targeting pathological gliosis seems to represent a valuable therapeutic approach. Compounds able to control glial activation with a combination of neuroprotective and anti‐inflammatory effects constitute a pool of possible therapeutic drugs to study. By using different in vitro and in vivo models of AD, I demonstrated the presence of important alterations of cerebral homeostasis caused by glial abnormalities.

Obtained results have contributed to clarify the possible consequences of glia activation and of the subsequent neuroinflammation, demonstrating the presence of significant (i) alterations of the cerebral cytoarchitecture, (ii) modifications of cerebral metabolism and (iii) neuronal death. My results support the notion that targeting pathological gliosis may represent a promising and innovative therapeutic approach for several brain diseases. However, the effect of therapeutic interventions targeting glial cells depends on reaching the perfect balance between attenuating the deleterious effects and maintain the beneficial mechanisms of brain defense.

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