Chromogranin peptides in Alzheimer's disease

Lechner, Thomas; Adlassnig, Christine; Humpel, Christian; Kaufmann, Walter A.; Maier, Hans; Reinstadler-Kramer, Karin; Hinterhölzl, Josef; Mahata, Sushil K.; Jellinger, K. A.; Marksteiner, Josef

doi:10.1016/j.exger.2003.09.018

Cited by 73 publications

(61 citation statements)

References 59 publications

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“…Distinct polymorphisms in the CGB gene could be assigned to schizophrenic individuals (Zhang et al, 2002;Iijima et al, 2004). In addition, other diseases like Alzheimer's disease (Marksteiner et al, 2000;Lechner et al, 2004) or temporal lobe epilepsy (Pirker et al, 2001) have been associated with changes in the cerebral CGB levels.…”

Section: Discussionmentioning

confidence: 99%

Inositol 1,4,5 trisphosphate receptor and chromogranin B are concentrated in different regions of the hippocampus

Nicolay

Hertle

Boehmerle

et al. 2007

J of Neuroscience Research

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Calcium (Ca 2+ ) release from intracellular stores plays a crucial role in many cellular functions in the brain. These intracellular signals have been shown to be transmitted within and between cells. We report a non-uniform distribution of proteins essential for Ca 2+ signaling in acutely prepared brain slice preparations and organotypic slice cultures, both made from rat hippocampus. The Type I inositol-1,4,5 trisphosphate receptor (InsP 3 R1) is the main InsP 3 R subtype in neurons. Immunohistochemistry experiments showed a prominent expression of InsP 3 R1 in the CA1 region of the hippocampus whereas the CA3 region and dentate gyrus (DG) showed only moderate immunoreactivity. In contrast, chromogranin B (CGB), a protein binding to the InsP 3 R1 on the luminal side of the endoplasmic reticular membrane was enriched in the CA3 region whereas DG and the CA1 region showed only faint CGB signals. The neuronal kinases leading to the formation of inositol-1,4,5 trisphosphate (InsP 3 ), phosphatidylinositol-4-kinase (PI4K), and phosphatidylinositol-4-phosphate-5-kinase (PIPK), showed strong immunoreactivity throughout all hippocampal cell fields with differences in the subcellular distribution. Moreover, a distinct band of strong CGB and PIPK immunoreactivity was observed in the CA3 region that coincides with the mossy fiber tract (stratum lucidum). These data show differential expression of the components of the signaling toolkit leading to InsP 3 -mediated Ca 2+ release in cells of the hippocampus. The regulation of these differences may play an important role in various neuropathologic conditions such as Alzheimer's disease, epilepsy, or schizophrenia. Keywords rat; intracellular signaling; calcium; immunohistochemistry; organotypic slice culture Calcium (Ca 2+ ) as an intracellular second messenger plays a crucial role in a variety of neuronal functions like development, excitability, neurotransmitter release, synaptic plasticity, gene transcription, and neurodegeneration (Berridge, 1998 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript side through voltage-gated, ligand-gated, and possibly store-operated channels (Berridge, 1998) or from internal stores through Ca 2+ channels in the endoplasmatic reticulum (ER), the Golgi apparatus, and the mitochondria (Rizzuto, 2001). The ER is the main intracellular calcium store and it is found throughout the cell (Spacek and Harris, 1997) forming a complex network (Terasaki et al., 1994;Berridge, 1998).Different Ca 2+ signals exhibit distinct temporal and spatial patterns. An increase of intracellular Ca 2+ can either be restricted to the site of Ca 2+ entry or spread throughout the neuron (Augustine et al., 2003). Because an increase in cytosolic Ca 2+ can cause a plethora of cellular effects, all Ca 2+ signals have to be regulated accurately (Usachev and Thayer, 1999). For this purpose, all neurons use a variety of channels, receptors, enzymes, and associated proteins that form a complex Ca 2+ signaling toolkit (Berridge et al., 2003). Th...

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Section: Discussionmentioning

confidence: 99%

Inositol 1,4,5 trisphosphate receptor and chromogranin B are concentrated in different regions of the hippocampus

Nicolay

Hertle

Boehmerle

et al. 2007

J of Neuroscience Research

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“…Western blot analysis of 100 ng rat b-amyloid(1-42) showed a strong single band of 4 kDa and a weaker band at 12 kDa under reducing or non-reducing conditions. Western blot analysis of 100 ng sbAPP protein showed a strong band of approximately 100 kDa under non-reducing conditions with the anti-APP A4 antibody, whereas no sbAPP-protein (1000 ng) was detectable with the anti-b-amyloid (17)(18)(19)(20)(21)(22)(23)(24) antibody. Brain slices incubated for 12 or 16 weeks at physiological pH tested conditions (pH 7.2 or pH 6.0, 7ApoE4, 2 weeks 371C) when the mix was loaded directly onto the gel.…”

Section: Effects Of Acidosis On Brain Slicesmentioning

confidence: 99%

“…Western blot of rat b-amyloid(1-42) and APP A4 Western Blot analysis for rat b-amyloid (17)(18)(19)(20)(21)(22)(23)(24) and sbAPP is shown in Figure 7. Western blot analysis of 100 ng rat b-amyloid(1-42) showed a strong single band of 4 kDa and a weaker band at 12 kDa under reducing or non-reducing conditions.…”

Section: Effects Of Acidosis On Brain Slicesmentioning

confidence: 99%

“…For the detection the Western Breeze Chromogenic System (Invitrogen) was used. Briefly, blots were blocked for 30 min with blocking buffer, then incubated for 90-180 min with the primary anti-b-amyloid (17)(18)(19)(20)(21)(22)(23)(24) antibody (Chemicon; 1:1000) or mouse anti-APP A4 (Chemicon MAB348; 1:2000), washed and incubated with alkaline phosphatase-conjugated anti-mouse IgG (Invitrogen) for 30-60 min at room temperature. After being washed, bound antibodies were visualized by p-nitro blue tetrazolium chloride and 5-bromo-4-chloro-3-indolyl phosphate (both Roche Molecular Biochemicals, Vienna, Austria).…”

Section: Western Blot Analysismentioning

confidence: 99%

“…Alzheimer brains were collected from postmortem patients, who fitted the NINCDS-ADRA clinical criteria of AD; the average age was 8178 years, the postmortem interval was 1574 h. 17 Tissue samples were taken from the dorsolateral, the orbifrontal and entorhinal cortex, and then immediately fixed by immersion in cold 4% paraformaldehyde in phosphate-buffered saline (PBS).…”

Section: Postmortem Alzheimer Brainmentioning

confidence: 99%

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Beta-amyloid expression, release and extracellular deposition in aged rat brain slices

Marksteiner

Humpel

2007

Mol Psychiatry

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Alzheimer's disease (AD) is characterized by b-amyloid plaques, tau pathology, cholinergic cell death and inflammation. The aim of this study was to investigate whether b-amyloid is generated, released and extracellularly deposited in organotypic brain slices. In developing slices, no amyloid-precursor protein (APP) was detectable; however, there was a strong upregulation in aging slices. In such slices, rat b-amyloid(1-42) and -(1-40) peptides were found using four sequence-specific antibodies. APP and b-amyloid were expressed in neurons and to a lesser extent in astrocytes. Beta-amyloid was secreted into the medium. Beta-amyloid was located extracellularly when aging slices were incubated with medium at pH 6.0 including apolipoprotein E4 (ApoE4). It is concluded that aging organotypic brain slices express bamyloid and that acidosis induces cell death with efflux of b-amyloid and extracellular depositions, which is triggered by ApoE4. This novel in vitro model may enable us to investigate further the pathological cascade for AD and may be useful to explore future therapeutics.

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Chromogranin A in the early steps of the neurosecretory pathway

2019

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Chromogranin A (CgA) is a soluble glycoprotein stored with hormones and neuropeptides in secretory granules (SG) of most (neuro)endocrine cells and neurons. Since its discovery in 1967, many studies have reported its structural characteristics, biological roles, and mechanisms of action. Indeed, CgA is both a precursor of various biologically active peptides and a granulogenic protein regulating the storage and secretion of hormones and neuropeptides. This review emphasizes the findings and theoretical concepts around the CgA‐linked molecular machinery controlling hormone/neuropeptide aggregation and the interaction of CgA‐hormone/neuropeptide aggregates with the trans‐Golgi membrane to allow hormone/neuropeptide targeting and SG biogenesis. We will also discuss the intriguing alteration of CgA expression and secretion in various neurological disorders, which could provide insights to elucidate the molecular mechanisms underlying these pathophysiological conditions.

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Chromogranin peptides in Alzheimer's disease

Cited by 73 publications

References 59 publications

Inositol 1,4,5 trisphosphate receptor and chromogranin B are concentrated in different regions of the hippocampus

Inositol 1,4,5 trisphosphate receptor and chromogranin B are concentrated in different regions of the hippocampus

Beta-amyloid expression, release and extracellular deposition in aged rat brain slices

Chromogranin A in the early steps of the neurosecretory pathway

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