A second cytotoxic proteolytic peptide derived from β-amyloid precursor protein

Lu, Daniel C.; Rabizadeh, Shahrooz; Shayya, Rana F.; Ellerby, Lisa M.; Salvesen, Guy S.; Koo, Edward H.; Bredesen, Dale E.

doi:10.1016/s0197-4580(00)83099-7

Cited by 116 publications

(231 citation statements)

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“…The b-amyloid precursor protein (APP) may also function as a dependence receptor: 103 it is cleaved intracytoplasmically at Asp664, releasing a cytotoxic peptide, APP-C31. The possibility that such an effect may play a role in the pathogenesis of Alzheimer's disease is discussed below.…”

Section: The Androgen Receptor As a Dependence Receptormentioning

confidence: 99%

“…Some of the recent findings in Alzheimer's disease are indeed compatible with such a notion: APP is cleaved in its intracytoplasmic region by caspases at Asp664, 104 and this cleavage releases a cytotoxic carboxyterminal fragment, APP-C31. 103 If this caspase cleavage event plays an important role in the pathogenesis of Alzheimer's disease, then the prevention of this cleavage should mitigate the behavioral and pathological alterations associated with the disease. Galvan et al 105 created transgenic mice carrying APP mutations characteristic of familial Alzheimer's disease, added a D664A mutation to prevent C31 formation, and then compared these mice to similar mice lacking the additional D664A mutation.…”

Section: The Androgen Receptor As a Dependence Receptormentioning

confidence: 99%

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Receptors that mediate cellular dependence

2005

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Cells depend for their survival on stimulation by trophic factors and other prosurvival signals, the withdrawal of which induces apoptosis, both via the loss of antiapoptotic signaling and the activation of proapoptotic signaling via specific receptors. These receptors, dubbed dependence receptors, activate apoptotic pathways following the withdrawal of trophic factors and other supportive stimuli. Such receptors may feature in developmental cell death, carcinogenesis (including metastasis), neurodegeneration, and possibly subapoptotic events such as neurite retraction and somal atrophy. Mechanistic studies of dependence receptors suggest that these receptors form ligand-dependent complexes that include specific caspases. Complex formation in the absence of ligand leads to caspase activation by a mechanism that is typically dependent on caspase cleavage of the receptor itself, releasing proapoptotic peptides. Cellular dependence receptors, considered in the aggregate, may thus form a system of molecular integration, analogous to the electrical integration system provided by dendritic arbors in the nervous system.

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Section: The Androgen Receptor As a Dependence Receptormentioning

confidence: 99%

Section: The Androgen Receptor As a Dependence Receptormentioning

confidence: 99%

Receptors that mediate cellular dependence

2005

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“…Amyloid intracellular domain or AICD (CTF57 and CTF59) can be produced by g-secretase (Yu et al, 2001a;Suh and Checler, 2002). CTF31 can be produced by caspases (Gervais et al, 1999;Lu et al, 2000). Increased production of h-amyloid peptide (Ah) has been thought to be involved in the pathogenesis of Alzheimer's disease (AD) (Steiner et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Progressive neuronal loss and behavioral impairments of transgenic C57BL/6 inbred mice expressing the carboxy terminus of amyloid precursor protein

Lee

Song

et al. 2006

Neurobiology of Disease

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“…Following caspase 3 activation, caspase 3 generates the carboxyl-terminally truncated fragment C31 from APP, which has been shown to be capable of apoptotic injury independent of caspase 3 [165]. Furthermore, caspase-dependent APP cleavage at D720 has also been observed in brains of Alzheimer's disease patients through demonstration of C31 expression [132].…”

Section: Processing Of App By Secretases and Caspasesmentioning

confidence: 99%

Stress in the brain: novel cellular mechanisms of injury linked to Alzheimer's disease

Chong

Maiese

2005

Brain Research Reviews

135

121

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More than a century has elapsed since the description of Alois Alzheimer's patient Auguste D. Yet, the well-documented generation of β-amyloid aggregates and neurofibrillary tangles that define Alzheimer's disease is believed to represent only a portion of the cellular processes that can determine the course of Alzheimer's disease. Understanding of the complex nature of this disorder has evolved with an increased appreciation for pathways that involve the generation of reactive oxygen species and oxidative stress, apoptotic injury that leads to nuclear degradation in both neuronal and vascular populations, and the early loss of cellular membrane asymmetry that mitigates inflammation and vascular occlusion. Recent work has identified novel pathways, such as the Wnt pathway and the serine-threonine kinase Akt, as central modulators that oversee cellular apoptosis and the formation of neurofibrillary tangles through their downstream substrates that include glycogen synthase kinase-3β, Bad, and Bcl-x L . Other closely integrated pathways control microglial activation, release of inflammatory cytokines, and caspase and calpain activation for the processing of amyloid precursor protein, tau protein cleavage, and presenilin disposal. New therapeutic avenues that are just open to exploration, such as with nicotinamide adenine dinucleotide modulation, cell cycle modulation, metabotropic glutamate system modulation, and erythropoietin targeted expression, may provide both attractive and viable alternatives to treat Alzheimer's disease.

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A second cytotoxic proteolytic peptide derived from β-amyloid precursor protein

Cited by 116 publications

References 0 publications

Receptors that mediate cellular dependence

Receptors that mediate cellular dependence

Progressive neuronal loss and behavioral impairments of transgenic C57BL/6 inbred mice expressing the carboxy terminus of amyloid precursor protein

Stress in the brain: novel cellular mechanisms of injury linked to Alzheimer's disease

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