Progressive brain dysfunction following intracerebroventricular infusion of beta1–42-amyloid peptide

Nakamura, Shizuo; Murayama, Norihito; Noshita, Takafumi; Annoura, Hirokazu; Ohno, Tomochika

doi:10.1016/s0006-8993(01)02704-4

Cited by 130 publications

(84 citation statements)

References 35 publications

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“…To identify the proteins that interact with A␤, we performed phage display screenings using A␤-(1-42), A␤-(25-35), A␤-(12-28), and A␤- (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). To account for the possibility that the binding site of the peptides might be hindered by binding of the peptide to the polystyrene plate, we also performed a solution screening with all four peptides.…”

Section: Resultsmentioning

confidence: 99%

“…Biochemical effects of A␤ include activation of calcium channels (4,5), inactivation of potassium channels (6), production of free radicals (7), excitotoxicity through activation of N-methyl-Daspartate receptors (8,9), inhibition of protein kinase C (10,11), and glutamate accumulation leading to increased Ca 2ϩ levels (12). Intracerebroventricular injection of A␤ produces impairment of spatial memory and non-spatial long term memory (13,14), reduction of protein kinase C activity (15), induction of apoptosis (13), and activation of astrocytes and microglia to release excessive amounts of inflammatory cytokines (16). Transgenic animals expressing human A␤ exhibit many of the pathologies of Alzheimer disease (AD), including cognitive deficits (17), age-related formation of amyloid plaques, activation of astrocytes and microglial cells, vascular amyloid pathology, degeneration of cholinergic nerve terminals, and reduced lifespan (18).…”

Section: ␤-Amyloid (A␤)mentioning

confidence: 99%

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Protection against β-Amyloid-induced Apoptosis by Peptides Interacting with β-Amyloid

Nelson

Alkon

2007

Journal of Biological Chemistry

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␤-Amyloid peptide produces apoptosis in neurons at micromolar concentrations, but the mechanism by which ␤-amyloid exerts its toxic effect is unknown. The normal biological function of ␤-amyloid is also unknown. We used phage display, coprecipitation, and mass spectrometry to examine the proteinprotein interactions of ␤-amyloid in normal rabbit brain in order to identify the biochemical receptors for ␤-amyloid. ␤-Amyloid was found to bind primarily to proteins involved in low density lipoprotein and cholesterol transport and metabolism, including sortilin, endoplasmic reticulum-Golgi intermediate compartment 2 (ERGIC2), ERGIC-53, steroid 5␣-reductase, and apolipoprotein B. ␤-Amyloid also bound to the C-reactive protein precursor, a protein involved in inflammation, and to 14-3-3, a protein that regulates glycogen synthase kinase-3␤, the kinase involved in tau phosphorylation. Of eight synthetic peptides identified as targets of ␤-amyloid, three were found to be effective blockers of the toxic effect of ␤-amyloid on cultured neuronal cells. These peptides bound to the hydrophobic region (residues 17-21) or to the nearby protein kinase C pseudo-phosphorylation site (residues 26 -30) of ␤-amyloid, suggesting that these may be the most critical regions for ␤-amyloid effector action and for aggregation. Peptides or other small molecules that bind to this region may protect against ␤-amyloid toxic effect by competitively blocking its ability to bind ␤-amyloid effector proteins such as sortilin and 14-3-3.

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Section: Resultsmentioning

confidence: 99%

Section: ␤-Amyloid (A␤)mentioning

confidence: 99%

Protection against β-Amyloid-induced Apoptosis by Peptides Interacting with β-Amyloid

Nelson

Alkon

2007

Journal of Biological Chemistry

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“…A burr hole was drilled in the skull, and the cannula (Alzet brain infusion kit II, Alza Scientific Products) was introduced into the right lateral ventricle at stereotaxic coordinates 0.6 mm posterior and 1.2 mm lateral to bregma and 4.0 mm deep to the pial surface. The cannula was held in place with cyanoacrylate, and the skin was sutured (Nakamura et al, 2001;Harrigan et al, 2002). Pumps were replaced after 28 d and connected to the same cannula.…”

Section: Methodsmentioning

confidence: 99%

Nogo Receptor Antagonism Promotes Stroke Recovery by Enhancing Axonal Plasticity

Lee¹,

Kim²,

Sivula³

et al. 2004

J. Neurosci.

327

297

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After ischemic stroke, partial recovery of function frequently occurs and may depend on the plasticity of axonal connections. Here, we examine whether blockade of the Nogo-NogoReceptor (NgR) pathway might enhance axonal sprouting and thereby recovery after focal brain infarction. Mutant mice lacking NgR or Nogo-AB recover complex motor function after stroke more completely than do control animals. After a stroke, greater numbers of axons emanating from the undamaged cortex cross the midline to innervate the contralateral red nucleus and the ipsilateral cervical spinal cord; this axonal plasticity is enhanced in ngr ؊/؊ or nogo-ab ؊/؊ mice. In rats with middle cerebral artery occlusion, both the recovery of motor skills and corticofugal axonal plasticity are promoted by intracerebroventricular administration of a function-blocking NgR fragment. Behavioral improvement occurs when therapy is initiated 1 week after arterial occlusion. Thus, delayed pharmacological blockade of the NgR promotes subacute stroke recovery by facilitating axonal plasticity.

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“…It is also implicated in the pathology of a number of severe neurodegenerative disorders such as glaucoma, motor neuron, and Alzheimer's, Parkinson's, and Huntington's diseases (1). There is evidence that a similar pathogenesis may contribute to neurodegenerative processes in these conditions (2), and that the extent of nerve cell loss is correlated with functional deficit (3)(4)(5)(6). If we could directly visualize this process, it would facilitate a much more precise diagnosis and critically enable accurate tracking of the disease state and the action of therapy.…”

mentioning

confidence: 99%

Real-time imaging of single nerve cell apoptosis in retinal neurodegeneration

Cordeiro

Guo

Luong

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

244

308

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Apoptotic nerve cell death is implicated in the pathogenesis of several devastating neurodegenerative conditions, including glaucoma and Alzheimer's and Parkinson's diseases. We have devised a noninvasive real-time imaging technique using confocal laserscanning ophthalmoscopy to visualize single nerve cell apoptosis in vivo, which allows longitudinal study of disease processes that has not previously been possible. Our method utilizes the unique optical properties of the eye, which allow direct microscopic observation of nerve cells in the retina. We have been able to image changes occurring in nerve cell apoptosis over hours, days, and months and show that effects depend on the magnitude of the initial apoptotic inducer in several models of neurodegenerative disease in rat and primate. This technology enables the direct observation of single nerve cell apoptosis in experimental neurodegeneration, providing the opportunity for detailed investigation of fundamental disease mechanisms and the evaluation of interventions with potential clinical applications, together with the possibility of taking this method through to patients.A poptosis is an orchestrated form of cell ''death by suicide.'' It is essential in both the development and normal maintenance of tissue function. It is also implicated in the pathology of a number of severe neurodegenerative disorders such as glaucoma, motor neuron, and Alzheimer's, Parkinson's, and Huntington's diseases (1). There is evidence that a similar pathogenesis may contribute to neurodegenerative processes in these conditions (2), and that the extent of nerve cell loss is correlated with functional deficit (3-6). If we could directly visualize this process, it would facilitate a much more precise diagnosis and critically enable accurate tracking of the disease state and the action of therapy. However, until now, it has not been possible to detect nerve cell apoptosis in vivo (1, 7-10).Annexin 5 is a protein that, in the presence of Ca 2ϩ , has a high affinity for phosphatidylserine (PS), an anionic phospholipid that is enriched in the inner leaflet of plasma membranes. The externalization of PS from the inner leaflet to the outer layer of the cell membrane is an invariant early feature in the apoptotic process that occurs before DNA fragmentation and nuclear condensation. Because of its properties, FITC-annexin 5 has become widely used in the cytological detection of cells undergoing apoptosis (11). More recently, annexin 5 has been shown to be effective in the identification of apoptosis in vivo by using radiological and macroscopic fluorescent techniques (7,8,10,12,13).However, existing in vivo techniques using annexin 5 either have been unable to resolve the process to a single cellular level (7-9) or require an invasive method performed under terminal anesthesia (10). Imaging the eye, compared with the rest of the body, offers a unique opportunity because of the presence of clear optical media allowing direct visualization of labeled disease processes as they occur. This mea...

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Progressive brain dysfunction following intracerebroventricular infusion of beta1–42-amyloid peptide

Cited by 130 publications

References 35 publications

Protection against β-Amyloid-induced Apoptosis by Peptides Interacting with β-Amyloid

Protection against β-Amyloid-induced Apoptosis by Peptides Interacting with β-Amyloid

Nogo Receptor Antagonism Promotes Stroke Recovery by Enhancing Axonal Plasticity

Real-time imaging of single nerve cell apoptosis in retinal neurodegeneration

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