The Inhibitory Effect of Apolipoprotein E4 on Neurite Outgrowth Is Associated with Microtubule Depolymerization

Nathan, Britto P.; Chang, Kung-Ching; Bellosta, Stefano; Brisch, Ellen; Ge, Nianfeng; Mahley, Robert W.; Pitas, Robert E.

doi:10.1074/jbc.270.34.19791

Cited by 249 publications

(188 citation statements)

References 47 publications

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“…The major role of apoE in the brain is the transport of lipid components which contribute to building up the myelin sheath. 30,31,32 In-vitro and in-vivo studies have shown that the apoE isoforms differentially modulate neuritic outgrowth, sprouting and branching 63,64,65 and the apoE4 isoform has been specifically associated with microtubule depolymerisation 65 and axonal degeneration 66 thus potentially affecting WM integrity. Although these studies point to a differential role for the apoE isoforms on white matter structure, the molecular mechanisms require further investigation.…”

Section: Discussionmentioning

confidence: 99%

The APOE ɛ4 allele modulates brain white matter integrity in healthy adults

et al. 2010

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The Apolipoprotein E (APOE) ε4 allele is the best-established genetic risk factor for sporadic Alzheimer's disease (AD) and is also associated with structural gray matter (GM) and functional brain changes in healthy young, middle-aged and elderly subjects. Because APOE is implicated in brain mechanisms associated with white matter (WM) development and repair, we investigated the potential role played by the APOE polymorphism on WM structure in healthy younger (age range: 20-35 years) and older (aged 50-78 years) adults using diffusion tensor imaging (DTI). General reduction of fractional anisotropy (FA) and increase in mean diffusivity (MD) values was found in carriers of the APOE ε4 allele relative to non-carriers. No significant interactions between genotype and age were observed, suggesting that differences in WM structure between APOE ε4-carriers and non-carriers do not undergo significant differential changes with age. This result was not explained by differences in brain morphology or cognitive measures. The APOE ε4 allele modulates brain WM structure before any clinical or neurophysiological expression of impending disease.

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Section: Discussionmentioning

confidence: 99%

The APOE ɛ4 allele modulates brain white matter integrity in healthy adults

et al. 2010

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“…Several studies have highlighted the critical role of apoE in brain plasticity after injury (in vivo and in vitro models) [6][7][8][9][10]. On the other hand, to date, few studies have addressed the importance of apoE during early postnatal development, although apoE mRNA has been shown to increase at birth, during suckling, and after fasting in the rat liver [11].…”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein E knockout mice have accentuated malnutrition with mucosal disruption and blunted insulin-like growth factor I responses to refeeding

et al. 2006

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Apolipoprotein E (apoE) is synthesized mainly in the liver and in the brain and is critical for cholesterol metabolism and recovery from brain injury. However, although apoE mRNA increases at birth, during suckling, and after fasting in rat liver, little is known about its role in early postnatal development. Using an established postnatal malnutrition model and apoE knock-out (ko) mice, we examined the role of apoE in intestinal adaptation responses to early postnatal malnutrition. Wild-type and apoE-ko mice were separated from their lactating dams for defined periods each day (4 hours on day 1, 8 hours on day 2, and 12 hours thereafter). We found significant growth deficits, as measured by weight gain or tail length, in the apoE-ko mice submitted to a malnutrition challenge, as compared with malnourished wild type, especially during the second week of postnatal development (P < .05). In addition, apoE-ko animals failed to show growth catch-up after refeeding, compared with wild-type malnourished controls. Furthermore, we found shorter crypts and reduced villus height and area in the apoE-ko malnourished mice, compared with controls, after refeeding. Insulinlike growth factor 1 expression was also blunted in the ileum in apoE-ko mice after refeeding, compared with wild-type controls, which exhibited full insulinlike growth factor 1 expression along the intestinal crypts, villi, and in the muscular layer. Taken together, these findings suggest the importance of apoE in coping with a malnutrition challenge and during the intestinal adaptation after refeeding. NIH Public Access

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“…In neuronal cells in culture the amount of apoE4 that enters the cells is less than that of apoE3. 7 We have therefore suggested a possible mechanism for the combined risk conveyed by HSV1 and apoE-ε4: that on stress or immunosuppression, reactivation of the latent HSV1 occurs in brain (if present) and the number of cells infected by the virus, and hence the extent of damage, is greater in apoE-ε4 possessors than in those with the other alleles. 1 The lack of involvement of apoE-ε4 in HSK contrasts with its apparent role in AD and in herpes labialis.…”

Section: Figure 1 Agarose Gel Electrophoresis Of Amplified Products Amentioning

confidence: 99%

Apolipoprotein E and herpes virus diseases: herpes simplex keratitis

Lin¹,

Tullo

Itzhaki³

1999

Eur J Hum Genet

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Our previous studies showed that herpes simplex type 1 virus (HSV1) is present in a high proportion of the brain of elderly normal people and Alzheimer's disease (AD) patients. We subsequently discovered that the combination of HSV1 in brain and carriage of the type 4 allele of the gene for apolipoprotein E (apoE-ε4) is a strong risk factor for AD, and also that apoE-ε4 is a strong risk factor for herpes labialis. In this study we have examined apoE genotypes of sufferers from another disorder caused by HSV1, namely, herpes simplex keratitis (HSK), to find if an apoE allele is involved in the disorder. In 46 HSK patients the apoE-ε4 allele frequency was 15%-the same as that found in 238 unaffected controls. The apoE-ε2 allele frequency was 13%-higher than the value of 7% for unaffected people, but the difference is not statistically significant.

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The Inhibitory Effect of Apolipoprotein E4 on Neurite Outgrowth Is Associated with Microtubule Depolymerization

Cited by 249 publications

References 47 publications

The APOE ɛ4 allele modulates brain white matter integrity in healthy adults

The APOE ɛ4 allele modulates brain white matter integrity in healthy adults

Apolipoprotein E knockout mice have accentuated malnutrition with mucosal disruption and blunted insulin-like growth factor I responses to refeeding

Apolipoprotein E and herpes virus diseases: herpes simplex keratitis

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