Oxidative Stress Increases Production of β-Amyloid Precursor Protein and β-Amyloid (Aβ) in Mammalian Lenses, and Aβ Has Toxic Effects on Lens Epithelial Cells

Frederikse, Peter H.; Garland, Donita; Zigler, J. Samuel; Piatigorsky, Joram

doi:10.1074/jbc.271.17.10169

Cited by 176 publications

(98 citation statements)

References 62 publications

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“…If Aβ is indeed aggregating in the AD lens, leading to these cataracts, it is possible that the initial molecular changes could be detected non-invasively as an early screening or diagnostic test. Further research is needed to establish the specificity of these cataracts and lens Aβ aggregations to AD, since both AβPP and Aβ have been shown to increase in concentration in the normal mammalian lens in response to UV radiation or other oxidative effects [109].…”

Section: (Figure 3)mentioning

confidence: 99%

Ocular Biomarkers for Early Detection of Alzheimer's Disease

Frost

Martins

Kanagasingam

2010

JAD

100

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Alzheimer's disease (AD) is the most common form of dementia and is characterized clinically by a progressive decline in memory, learning and executive function and neuropathologically by the presence of cerebral amyloid deposits. Despite a century of research, there is still no cure or conclusive pre-mortem diagnosis for the disease. A number of symptom-modifying drugs for AD have been developed, but their efficacy is minimal and short-lived. AD cognitive symptoms arise only after significant, irreversible neural deterioration has occurred, hence there is an urgent need to detect AD early, before the onset of cognitive symptoms. An accurate, early diagnostic test for AD would enable current and future treatments to be more effective, as well as contribute to the development of new treatments.While most AD related pathology occurs in the brain, the disease has also been reported to affect the eye, which is more accessible for imaging than the brain. AD-related proteins exist in the normal human eye and may produce ocular pathology in AD. There is some homology between the retinal and cerebral vasculatures and the retina also contains nerve cells and fibers that form a sensory extension of the brain. The eye is the only place in the body where vasculature or neural tissue is available for non-invasive optical imaging. This article presents a review of current literature on ocular morphology in AD and discusses the potential for an ocular based screening test for AD.

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Section: (Figure 3)mentioning

confidence: 99%

Ocular Biomarkers for Early Detection of Alzheimer's Disease

Frost

Martins

Kanagasingam

2010

JAD

100

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“…For example, Paola et al 25 and Frederikse et al 26 reported that intracellular Ab production increased as a result of oxidative stress in culture systems. In addition, Aplet et al 27 established the correlation between aging-related increases in oxidative stress and b-secretase activity with Ab plaque formation in a mouse model of AD.…”

Section: Discussionmentioning

confidence: 99%

DNA damage-inducing agents elicit γ-secretase activation mediated by oxidative stress

et al. 2008

Cell Death Differ

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According to the amyloid cascade hypothesis, Alzheimer's disease is the consequence of neuronal cell death induced by b-amyloid (Ab), which accumulates by abnormal clearance or production. On the other hand, recent studies have shown cell death-induced alteration in amyloid precursor protein (APP) processing, suggesting potential mutual interactions between APP processing and cell death. We have shown previously that the cell death caused by DNA damage-inducing agents (DDIAs) facilitated c-secretase activity and Ab generation in a Bax/Bcl-2-dependent, but caspase-independent manner. Here, we attempted to elucidate the downstream mechanism that modulates c-secretase activity in DDIA-treated cells. N-acetyl cysteine, a potent antioxidant, attenuated DDIA-induced enhancement of c-secretase activity but failed to rescue cell death. Overexpression of heat shock protein 70, which blocks cytochrome c release from mitochondria, also reduced c-secretase activity. Moreover, glutathione depletion significantly facilitated c-secretase activity and Ab generation by enhancing the formation of higher molecular weight c-secretase complex before signs of cell death developed. Finally, Ab treatment, a known inducer of oxidative stress, also increased c-secretase activity. Taken together, these results indicate that DDIA-induced c-secretase activation is dependent on augmented oxidative stress, and that Ab and c-secretase may activate each other. On the basis of these results, we propose a feed-back loop between oxidative stress and Ab generation mediated by c-secretase activation.

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“…The crystalline lens also could be involved in AD, and high levels of β-amyloid were described in lens epithelia of subjects with a particular and rare type of cataract, the anterior subcapsular cataract [73,74]. Other authors have investigated possible changes in retinal anatomy in patients with AD, reporting an abnormal reduction of retinal thickness (by OCT) [75] associated with defective blood flow [76].…”

Section: Alzheimer' Disease and Eye Pathologiesmentioning

confidence: 99%

“…The crystalline lens also could be involved in AD, and high levels of β-amyloid were described in lens epithelia of subjects with a particular and rare type of cataract, the anterior subcapsular cataract [73,74] in the number of optic nerve fibers, probably due to the toxicity on RGCs of β-amyloid, has been detected in some studies [78][79][80].…”

Section: Alzheimer' Disease and Eye Pathologiesmentioning

confidence: 99%

“…pilocarpine) drugs [59][60][61][62][63][64][65][66][67]. Some have even proposed that this altered response could be pathognomonic of AD [68][69][70][71] while others have refuted this hypothesis as non-specific [72].The crystalline lens also could be involved in AD, and high levels of β-amyloid were described in lens epithelia of subjects with a particular and rare type of cataract, the anterior subcapsular cataract [73,74] in the number of optic nerve fibers, probably due to the toxicity on RGCs of β-amyloid, has been detected in some studies [78][79][80]. …”

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Critical Review on the Relationship between Glaucoma and Alzheimer's Disease

Pescosolido¹,

Pascarella²,

Buomprisco³

et al. 2014

AOVS

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two distinct pathologies, despite similar pathophysiology and demographic distribution. Both diseases are neurodegenerative, chronic and progressive in nature, with irreversible neuronal cell loss. Furthermore, both POAG and AD disease primarily affect the elderly, with a strongly age-dependent incidence. The progressive debilitating course of both diseases has tremendous implications on an aging population [1]. For years Glaucoma has been associated with high IOP [2], although scientists had accepted this etiology with caution, since it was known that POAG could develop in subjects with normal or even low IOP. In fact, one out of three POAG patients has normotensive or low tension glaucoma [3]. This observation has led the scientific community to look for other possible causes of this slowly debilitating pathogenesis.The hallmark of neurodegenerative diseases is the death of specific neuron populations, and of those other neurons that are inter-connected and depend for their survival on the inputs from the main population (trans-synaptic degeneration). In Parkinson's disease accumulation of alfa-synuclein [4] causes the degeneration of dopaminergic neurons of the substantia nigra, in the midbrain, thus leading to the classic symptoms of Parkinson's such as tremor, akinesia, bradykinesia, and stiffness [5]. In AD there is a loss of neurons in the cerebral cortex and certain subcortical regions. This loss results in gross atrophy of the affected regions, including degeneration in the temporal lobe and parietal lobe, and parts of the frontal cortex and cingulate gyrus [6]. Both amyloid plaques and neurofibrillary tangles are AbstractA third of people affected by primary open angle glaucoma (POAG) have normal or even low intraocular pressure (IOP), such as in the case of normotensive glaucoma and low pressure glaucoma. Therefore, high IOP, while remaining the most important risk factor for POAG development, is not the only one. POAG has been recognized to belong to the class of neurodegenerative diseases, such as Alzheimer's (AD) and Parkinson's, and several recent studies have suggested possible links between Alzheimer's and glaucoma both from an epidemiological and a pathogenetic point of view. In fact, several pathogenetic factors are common between the two diseases: the diffuse axonal degeneration of ganglion cells, the presence of specific markers (such as amyloid-β) in the aqueous humor, the activation of caspases and the abnormal processing of amyloid precursor protein in retinal ganglion cells, the reduction of the intracranial pressure of the cerebrospinal fluid, the mutations of the gene that encodes for optineurine. Conflicting data have been reported concerning apolipoprotein E. Finally, numerous publications affirm the utility of molecules traditionally used in the treatment of neurodegenerative diseases (e.g. forskolin, L-carnosine, homotaurine, folic acid, acetylcholinesterase inhibitors, antioxidant vitamins, glatiramer acetate, etc.) also in the treatment of glaucoma.In the present research we ana...

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Oxidative Stress Increases Production of β-Amyloid Precursor Protein and β-Amyloid (Aβ) in Mammalian Lenses, and Aβ Has Toxic Effects on Lens Epithelial Cells

Cited by 176 publications

References 62 publications

Ocular Biomarkers for Early Detection of Alzheimer's Disease

Ocular Biomarkers for Early Detection of Alzheimer's Disease

DNA damage-inducing agents elicit γ-secretase activation mediated by oxidative stress

Critical Review on the Relationship between Glaucoma and Alzheimer's Disease

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