Microglial chemotaxis, activation, and phagocytosis of amyloid β-peptide as linked phenomena in Alzheimer's disease

Neuroprotective properties of the innate immune system and bone marrow stem cells in Alzheimer's disease

“…The notion that microglial cells are able to phagocytose amyloid deposits has been supported in previous reports. [95][96][97] The LPS receptor CD14 seems to be a key component in the recognition of b-amyloid and the induction of phagocytosis by microglial cells. 97 Unfortunately, most of the results supporting microglial phagocytosis of b-amyloid have been obtained from in vitro studies, whereas in vivo data confirming this process have not been provided until recently.…”

Neuroprotective roles of the P2Y2 receptor

“…Recruitment of activated microglia to sites of inflammation enhances the phagocytosis of aggregated Aβ via the F c receptor [222,223]. Studies have shown that microglial cells exposed to Aβ release ATP [75,224]. Our recent data indicate that primary microglial cells exposed to oligomeric Aβ 1-42 have 3-4-fold increased levels of TNF-α and IL-1β release, as compared to control cells without Aβ 1-42 treatment (Table 3).…”

“…Data represent means ± SEM (n03) **p<0.01 indicates a significant difference from untreated control diapedesis of neutrophils toward LPS required Rho kinase activity and was potentiated by treatment with UTP [102]. Nucleotides are released from leukocytes migrating toward chemoattractants [239], including Aβ 1-42 [224], and increased expression of P2Y 2 Rs in vascular endothelium of damaged tissue [244] regulates nucleotide-induced increases in [Ca 2+ ] i , phosphorylation of myosin light chain, and activation of Rho kinases [24,95]. Thus, it seems plausible that the P2Y 2 R in microvascular endothelium of the brain should contribute to monocyte binding, diapedesis, and accumulation of bone marrow-derived microglia around brain tissue burdened with Aβ plaques whereupon the loss of this mechanism should limit Aβ clearance and proinflammatory neuroprotection in the AD brain.…”

A doença de Alzheimer: aspectos fisiopatológicos e farmacológicos

“…As células da micróglia ativadas também foram abundantes nos cérebros de pacientes portadores da doença de Alzheimer e produziram uma variedade de compostos neurotóxicos, incluindo radicais superóxidos, glutamato e óxido nítrico 43 . Mais ainda, a exposição da micróglia à substância Aβ levou à liberação de fatores pró-inflamatórios, incluindo a interleucina-1 (IL-1), a interleucina-6 (IL-6), a interleucina-8 (IL-8) e o fator de necrose tumoral (TNF-α) 44 .…”