118-120 To summarize, if inflammatory activation of astrocytes
unquestionably has consequences for neuronal function and viability, it must be emphasized that the overall effect is dependent on the fine balance between a number of factors including the type, duration, and severity of the insult, the complex interplay between the various cytokines released by astrocytes and surrounding cells, and the receptors for cytokines and growth factors expressed by these neighboring cells. Alzheimer’s disease #Enzastaurin keyword# Alzheimer’s disease (AD), the most prevalent neurodegenerative disorder, is characterized by the progressive decline of cognitive functions including memory and mental processing, and by disturbances in behavior and personality.121 Typical histopathological features of the Inhibitors,research,lifescience,medical AD brain are amyloid-β (Aβ) plaques which may contain dystrophic neurites, intracellular neurofibrillary tangles, vascular amyloidosis, neuronal and synaptic loss, and reactive gliosis.
Though the exact pathophysiological mechanisms Inhibitors,research,lifescience,medical leading to synaptic loss and the resulting cognitive decline have not been fully elucidated, a central role of Aβ peptides in concert with neuroinflammation is generally accepted.122 Alois Alzheimer himself in 1910 suggested that glial cells may participate in the pathogenesis of dementia123; however, their exact role is still a matter of debate, as available Inhibitors,research,lifescience,medical evidence can argue both for neuroprotective or neurotoxic effects. Reactive astrocytes, like microglia, are observed in close association with Aβ plaques in the brains of AD patients,124,125 and both cell types have been shown to be capable of internalizing and degrading Aβ peptides.126-128 This is thought to be a neuroprotective mechanism
by contributing to the clearance of Aβ from the extracellular space, thus avoiding the accumulation of toxic extracellular Aβ. Several observations support an active role of astrocytes in Aβ clearance. Inhibitors,research,lifescience,medical For example, astrocytes surrounding plaques in autopsy material from the brain of AD patients contain intracellular Aβ deposits.128,130 In addition, when exogenous astrocytes were of transplanted into the brain of Aβ plaque-bearing transgenic mice, they migrated towards Aβ deposits and internalized Appositive material.129 Similarly in ex vivo studies, binding, internalization, and degradation of Aβ could be observed when cultured astrocytes were seeded on top of plaque-bearing sections prepared either from the brains of AD patients or transgenic mice models of AD.127,129 The physiological importance of Aβ clearance by glial cells in vivo is evidenced by the increased Ap accumulation and premature death observed in a transgenic mouse model of AD when microglial activation was impaired.