Transcription factor NF-κB is activated in primary neurons by amyloid β peptides and in neurons surrounding early plaques from patients with Alzheimer disease

Abstract

ABSTRACT

Inflammatory Signals Induce Neurotrophin Expression in Human Microglial Cells

“…In addition, in contrast to A/I(25-35), the A/3(i-40) and A/I(1-42) fragments, known to elicit microglial neurotoxicity (Giulian et al, 1996), did not affect microglial NT synthesis (Fig. 5).The factthat A/I( 25-35) did not enhance microglial NGF expression at a dose higher than 30~.tg/ml(data not shown) is in agreement with the observation of an inverted U-shaped concentration curve elicited by A/I(25-35)-induced NF-KB activation in primary neurons (Kaltschmidt et al, 1997).Previously, it has been reported that A/I( 25-35) activated NF-KB in microglial cells (Yan et al, 1996), rat cerebellar granule neurons, and astrocytes (Kaltschmidt et al, 1997), which prompted us to examine whether NF-KB is involved in A/3(25-35)-induced microglial NGF synthesis. Figure 6 shows that microghal NF-KB activation by A/3(25-35) several microglial antigens.…”

“…Previously, it has been reported that A/I( 25-35) activated NF-KB in microglial cells (Yan et al, 1996), rat cerebellar granule neurons, and astrocytes (Kaltschmidt et al, 1997), which prompted us to examine whether NF-KB is involved in A/3(25-35)-induced microglial NGF synthesis. Figure 6 shows that microghal NF-KB activation by A/3(25-35) several microglial antigens.…”

“…J. Neurochem. 70, 699-707 (1998).ing free oxygen intermediates, proteases, excitatory amino acids, arachidonic acid derivatives, and cytokines, and have been implicated in the destruction of neurons in trauma (Banati et al, 1993;Thanos et al, 1993), Alzheimer's disease (McGeer et al, 1987(McGeer et al, , 1993 Giulian et al, 1995Giulian et al, , 1996McGeer and McGeer, 1995;Kaltschmidt et al, 1997), and human immunodeficiency virus infection (Giulian et al, 1990;Dickson et al, 1993). Moreover, in vitro studies have revealed that microglia/brain macrophages can secrete growth factors [e.g., basic fibroblast growth factor and nerve growth factor (NGF) 1~known to enhance survival and fiber outgrowth of different types of CNS neurons Mallat et al, 1989;Shimojo et al, 1991;Araujo and Cotman, 1992;Elkabes et al, 1996).…”

Biphasic Role of Nuclear Factor-k B on Cell Survival and COX-2 Expression in SOD1 Tg Astrocytes after Oxygen Glucose Deprivation

“…Evidence for NF-kB activation has also been reported in important examples of neurodegeneration, such as Alzheimer's disease (Kaltschmidt et al, 1997;Akama et al, 1998) and Parkinson's disease (Hunot et al, 1997). Zhang et al (2005) recently observed that neuronal activation of NF-kB in cerebral ischemia contributed to ischemic brain damage in vivo.…”

Roles for NF-κB in nerve cell survival, plasticity, and disease

“…Levels of p65 immunoreactivity are increased in neurons and astrocytes associated with amyloid plaques in the brains of Alzheimer's disease patients suggesting increased NF-kB activation in those cells. 74 Exposure of cultured neurons to amyloid b-peptide or a secreted form of amyloid precursor protein (sAPP) induced NF-kB activation, 13,75 suggesting a role for proteolytic products of APP in NF-kB activation in Alzheimer's disease brain cells. Levels of NF-kB activity are increased in cholinergic neurons in the basal forebrain of Alzheimer's patients.…”