Expression of ErbB4 in the apoptotic neurons of Alzheimer's disease brain

Abstract

Neuregulin-1 (NRG1) signaling participates in the synaptic plasticity, maintenance or regulation of adult brain. Although ErbB4, a key NRG1 receptor, is expressed in multiple regions in the adult animal brain, little is known about its localization in Alzheimer's disease (AD) brains. We previously reported that ErbB4 immunoreactivity showed regional difference in the hippocampus of age-matched control. In the present paper, immunohistochemical characterization of the distribution of ErbB4 receptor in the hippocampus relative to pathology staging were performed in age-matched control (Braak stage 0, n=6) and AD (Braak stage I/V, n=10). Here, we found that ErbB4 immunoreactivity was significantly increased in apoptotic hippocampal pyramidal neurons in the brains of AD patients, compared to those of age-matched control subjects. In AD brains, ErbB4 immunoreactivity was demonstrated to colocalize with the apoptotic signal Bax in apoptotic hippocampal pyramidal neurons. These results suggest that up-regulation of ErbB4 immunoreactivity in apoptotic neuron may involve in the progression of pathology of AD.

Fumanjian, a Classic Chinese Herbal Formula, Can Ameliorate the Impairment of Spatial Learning and Memory through Apoptotic Signaling Pathway in the Hippocampus of Rats with Aβ1–40‐Induced Alzheimer’s Disease

“…The interaction between the antiapoptotic protein Bcl-2 and the proapoptotic protein Bax plays a key role in the activation of intrinsic apoptotic signals involving mitochondria which secondary release cytochrome C and the activation of intracellular cysteine proteases, particularly caspase-9 and caspase-3. The initiator caspase-9 is activated and can initiate the activation of executioner caspase, mainly caspase-3, resulting in cell destruction by proteolysis [25]. In the present study, we presented evidences that the neuronal damage induced by infusing A β 1–40 into hippocampus proceeded through apoptotic signaling pathway and FMJ attenuated apoptotic-like changes.…”

Dopamine Burden Triggers Neurodegeneration via Production and Release of TNF-α from Astrocytes in Minimal Hepatic Encephalopathy

“…Interaction between the antiapoptotic protein Bcl-2 and the proapoptotic protein Bax plays a key role in the activation of intrinsic apoptotic signals involving the mitochondria, which secondarily release cytochrome c, and the activation of intracellular cysteine proteases, particularly caspase-9 and caspase-3. The initiator caspase-9 is activated and can initiate the activation of executioner caspase, mainly caspase-3, resulting in cell destruction by proteolysis [53]. We found that PCN-enriched cultures have no PCAs in co-cultivation in response to DA, where apoptosis is expressed rather sparsely and is more difficult to induce.…”

Analysis of Copy Number Variation in Alzheimer’s Disease: The NIALOAD/ NCRAD Family Study

“…NRG1 and ErbB4 immunoreactivity have been found to be associated with neuronal plaques in AD brains as well in a transgenic mouse model of AD [66]. A significant increase in ErbB4 immunoreactivity was also observed in AD human brains, and this was demonstrated to colocalize with the apoptotic signal Bax in apoptotic hippocampal pyramidal neurons, suggesting the possible role of NRG1/ErbB4 signaling as a survival signal in AD progression [67]. The authors in a more recent study showed that the immunoreactivities of ErbB4 and phospho-ErbB4 were of higher intensity in the neurons of the CA1-2 transitional field of AD brains compared to age-matched controls [68].…”