An intracellular protein that binds amyloid-β peptide and mediates neurotoxicity in Alzheimer's disease

  title={An intracellular protein that binds amyloid-$\beta$ peptide and mediates neurotoxicity in Alzheimer's disease},
  author={Shi Du Yan and Jin Fu and Claudio Soto and Xi Chen and Huaijie Zhu and Futwan Al-Mohanna and Kate S Collison and Aiping Zhu and Eric Stern and Takaomi C. Saido and Masaya Tohyama and Satoshi Ogawa and Alex E. Roher and David M. Stern},
Amyloid-β is a neurotoxic peptide which is implicated in the pathogenesis of Alzheimer's disease. It binds an intracellular polypeptide known as ERAB, thought to be a hydroxysteroid dehydrogenase enzyme, which is expressed in normal tissues, but is overexpressed in neurons affected in Alzheimer's disease. ERAB immunoprecipitates with amyloid-β, and when cell cultures are exposed to amyloid-β, ERAB inside the cell is rapidly redistributed to the plasma membrane. The toxic effect of amyloid-β on… 

The consequences of mitochondrial amyloid beta-peptide in Alzheimer's disease.

The present review explores the possible mechanisms by which cell death occurs, considering the evidence presented on a molecular, cellular and in vivo level.

Amyloid-β peptide binds to microtubule-associated protein 1B (MAP1B)

Neurotoxicity of the Alzheimer’s β-Amyloid Peptide

How many microscopic and spectroscopic techniques have been used in attempts to understand the Aβ fibrillization process and to provide a means of generating agents capable of halting Aβ deposition and hence disease progression in AD is explored.

Phosphorylated amyloid-beta: the toxic intermediate in alzheimer's disease neurodegeneration.

  • N. Milton
  • Biology, Chemistry
    Sub-cellular biochemistry
  • 2005
The results from this study suggest that Abeta phosphorylation could play a role in AD pathology and represent a novel therapeutic target and Cannabinoids prevented phosphorylated Abeta toxicity.

Mitochondrial β-amyloid in Alzheimer's disease.

By using a modified peptide approach it is possible to reverse the expression of these two proteins in living transgenic animals and also to recover mitochondrial and behavioural deficits, indicating that the ABAD-Aβ interaction is potentially an interesting target for therapeutic intervention.

β-Amyloid Peptide-induced Apoptosis Regulated by a Novel Protein Containing a G Protein Activation Module*

It is suggested that BBP is a target of neurotoxic β-amyloid peptide and provide new insight into the molecular pathophysiology of Alzheimer's disease.

The activity of amyloid beta binding alcohol dehydrogenase in Alzheimer's disease

It is shown that by using a modified peptide approach it is possible to reverse the expression of these two proteins in living transgenic animals and also to recover mitochondrial and behavioural deficits, indicating that the ABAD–Aβ interaction is potentially an interesting target for therapeutic intervention.

Amyloid-β Peptide Binds to Cytochrome C Oxidase Subunit 1

It is shown for the first time that Aβ 1–42 bound to a peptide comprising the amino-terminal region of cytochrome c oxidase subunit 1, which may explain, in part, the diminished enzymatic activity of respiratory chain complex IV and subsequent neuronal metabolic dysfunction observed in AD.

Beta-amyloid oligomers: recent developments

A review of recent findings on the toxic effects of amyloid-β oligomers, their physico-chemical properties and the possible pathways of their formation in vitro and in vivo is discussed.

Amyloid toxicity in Alzheimer’s disease

Reconfiguring this process to disfavor amyloid generation might be possible through the reduction of APP or inhibition of enzymes that convert the precursor protein to amyloids.



RAGE and amyloid-β peptide neurotoxicity in Alzheimer's disease

Evidence is presented that the 'receptor for advanced glycation end products' (RAGE) is such a receptor, and that it mediates effects of the peptide on neurons and microglia and indicates that it is relevant to the pathogenesis of neuronal dysfunction and death.

Neurotoxicity of a fragment of the amyloid precursor associated with Alzheimer's disease.

A peptide derived from the amyloid precursor may be neurotoxic, and conditioned medium from these cells was toxic to neurons in primary hippocampal cultures, and the toxic agent could be removed by immunoabsorption with an antibody directed against theAmyloid polypeptide.

Neurotrophic and neurotoxic effects of amyloid beta protein: reversal by tachykinin neuropeptides.

The amyloid beta protein could function as a neurotrophic factor for differentiating neurons, but at high concentrations in mature neurons, as in Alzheimer's disease, could cause neuronal degeneration.

Intracellular accumulation and resistance to degradation of the Alzheimer amyloid A4/beta protein.

It is reported that a 42-residue synthetic peptide, beta 1-42, corresponding to one of the longer forms of the A4/beta protein, accumulates in cultured human skin fibroblasts and is stable for at least 3 days, and suggests that relatively nonspecific proteolysis may be sufficient to generate the A 4/ beta protein if this part of APP is selectively resistant to proteolytic.

Intracellular and secreted Alzheimer beta-amyloid species are generated by distinct mechanisms in cultured hippocampal neurons.

It is shown that hippocampal neurons are able to utilize an alternate pathway to produce intracellular beta A4, and a common feature of two types of APP mutations implicated in early-onset AD is their increased production of C-terminally elongatedbeta A4 (beta 42), both intra- and extracellularly.

Hydrogen peroxide mediates amyloid β protein toxicity

Degeneration in vitro of post-mitotic neurons overexpressing the Alzheimer amyloid protein precursor

The results suggest that post-mitotic neurons are vulnerable to overexpressed APP, which undergoes aberrant processing to generate potentially amyloidogenic fragments.

A model for beta-amyloid aggregation and neurotoxicity based on free radical generation by the peptide: relevance to Alzheimer disease.

Evidence is presented that beta-amyloid fragments, at concentrations that previously have been shown to be neurotoxic to cultured neurons, can inactivate oxidation-sensitive glutamine synthetase and creatine kinase enzymes and generate free radical peptides.