Abnormalities in cholesterol metabolism cause peripheral neuropathy and dementia in AIDS—A hypothesis

Falkenbach, A.; Klauke, Stephan; Althoff, P.-H.

doi:10.1016/0306-9877(90)90085-s

Cited by 11 publications

(6 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Notably, low levels of HDL and high levels of triglycerides suggest that the RCT branch of cholesterol metabolism may be affected. Consistent with this hypothesis, Falkenbach et al [153] found clin-ical and histopathological similarities between AIDS and Tangier disease, a classical disorder of RCT. Recently, it was demonstrated that a decline in HDL levels in treatmentnaïve patients correlated with the HIV viral load [154], supporting the direct role of HIV infection in impairment of cholesterol metabolism.…”

Section: Hiv Infection and Cholesterol Metabolismmentioning

confidence: 79%

The macrophage: the intersection between HIV infection and atherosclerosis

Crowe

Westhorpe

Mukhamedova

et al. 2009

Journal of Leukocyte Biology

130

124

View full text Add to dashboard Cite

HIV-infected individuals are at increased risk of coronary artery disease (CAD) with underlying mechanisms including chronic immune activation and inflammation secondary to HIV-induced microbial translocation and low-grade endotoxemia; direct effects of HIV and viral proteins on macrophage cholesterol metabolism; and dyslipidemia related to HIV infection and specific antiretroviral therapies. Monocytes are the precursors of the lipid-laden foam cells within the atherosclerotic plaque and produce high levels of proinflammatory cytokines such as IL-6. The minor CD14+/CD16+ "proinflammatory" monocyte subpopulation is preferentially susceptible to HIV infection and may play a critical role in the pathogenesis of HIV-related CAD. In this review, the central role of monocytes/macrophages in HIV-related CAD and the importance of inflammation and cholesterol metabolism are discussed.

show abstract

Section: Hiv Infection and Cholesterol Metabolismmentioning

confidence: 79%

The macrophage: the intersection between HIV infection and atherosclerosis

Crowe

Westhorpe

Mukhamedova

et al. 2009

Journal of Leukocyte Biology

130

124

View full text Add to dashboard Cite

show abstract

“…Recently, abnormalities in the levels and metabolism of apoE and apoA-I in peripheral nerve have been proposed to cause or contribute to a variety of peripheral neuropathies, including human immunodeficiency virus neuropathy (Falkenbach et al ., 1990), alcoholic neuropathy (Lin et al ., 1992), and diabetic neuropathy (Ishibashi et al ., 1993) . Furthermore, Tangier disease, a familial disorder characterized by extremely low serum levels of apoA-1 and accumulation of cholesteryl esters in many cell types, frequently manifests a peripheral neuropathy .…”

Section: Discussionmentioning

confidence: 99%

“…Greatly elevated levels of apoE and A-I, as well as other apolipoproteins, are found in animal models of Wallerian degeneration or demyelinating neuropathy, and in humans with either axonal or demyelinating neuropathies (Ignatius et al ., 1986 ;Snipes et al ., 1986 ;Boyles et al ., 1990 ;Spreyer et al ., 1990 ;Gelman et al ., 1991) . Because of this apparent role of apoE and apoA-1 in nerve repair, abnormalities in the levels and metabolism of these apolipoproteins in peripheral nerve have been proposed to cause or contribute to a variety of peripheral neuropathies (Falkenbach et al ., 1990 ;Lin et al ., 1992 ;Ishibashi et al ., 1993) .…”

mentioning

confidence: 99%

Nerve Regeneration and Cholesterol Reutilization Occur in the Absence of Apolipoproteins E and A‐I in Mice

Goodrum

Bouldin²,

Zhang³

et al. 1995

Journal of Neurochemistry

View full text Add to dashboard Cite

Apolipoproteins have been implicated in the salvage and reutilization of myelin cholesterol during Wallerian degeneration and the subsequent nerve regeneration. Current evidence suggests that myelin cholesterol complexes with apolipoproteins E and A‐I to form lipoproteins that are taken up via low‐density lipoprotein receptors on myelinating Schwann cells. We recently reported, however, that apolipoprotein E is not required for nerve regeneration or reutilization of myelin cholesterol. We have now investigated nerve regeneration and the reutilization of cholesterol in mutant mice deficient in both apolipoproteins E and A‐I. Morphologic examination of nerves 4 and 12 weeks after crush injury revealed that regeneration proceeded at a normal rate in the absence of these apolipoproteins. Autoradiography of regenerating nerves indicated that prelabeled myelin lipid was reutilized in the regenerating myelin. 3‐Hydroxy‐3‐methylglutaryl‐CoA reductase, the rate‐limiting enzyme in cholesterol synthesis, was down‐regulated in the regenerating nerves, indicative of cholesterol uptake via lipoproteins. Prelabeled myelin cholesterol was present in lipoprotein fractions isolated from crushed nerves of mutant mice. These data suggest that there is considerable redundancy in the process of cholesterol reutilization within nerve, and that apolipoproteins other than apolipoproteins E and A‐I may be involved in the recycling of myelin cholesterol.

show abstract

“…Abnormalities in the level and metabolism of these apolipoproteins in the peripheral nerve have been correlated with a variety of peripheral neuropathies (44,45). However, recent studies of mice lacking a functional apoE gene (20) or containing disrupted genes for both apoE and apoA-I (21) revealed that neither apoE nor apoA-I are required for nerve regeneration and that cholesterol reutilization in these animals continues to be mediated by endoneurial lipoproteins.…”

Section: Discussionmentioning

confidence: 99%

Role of Lipoproteins in the Delivery of Lipids to Axons during Axonal Regeneration

Chaves

Rusiñol

Vance

et al. 1997

Journal of Biological Chemistry

174

131

View full text Add to dashboard Cite

Nerve fiber elongation involves the input of lipids to the growing axons. Since cell bodies are often a great distance from the regenerating tips, alternative sources of lipids have been proposed. We previously demonstrated that axonal synthesis of phosphatidylcholine is required for axonal growth ( We now show that when compartmented cultures of rat sympathetic neurons are incubated with pravastatin, in the absence of exogenously supplied lipids, cholesterol synthesis is inhibited and axonal growth is impaired. The addition of cholesterol to the axons or cell bodies of neurons treated with this inhibitor restores normal axonal elongation. Similarly, a supply of cholesterol via lipoproteins restores normal axonal growth. In contrast, lipoproteins do not provide axons with sufficient phosphatidylcholine for normal elongation when axonal phosphatidylcholine synthesis is inhibited. Thus, our studies support the idea that during axonal regeneration lipoproteins can be taken up by axons from the microenvironment and supply sufficient cholesterol, but not phosphatidylcholine, for growth. We also show that neither apoE nor apoA-I within the lipoproteins is essential for axonal growth.During nerve regeneration, large amounts of lipids are required for remyelination and expansion of axonal membranes. Synthesis of new myelin by Schwann cells in the regenerating peripheral nerve has been extensively studied (1-4). An interesting model for regeneration of injured peripheral nerve, involving apolipoprotein E (apoE) 1 and the coordinated storage and redistribution of cholesterol, has been proposed (5) and supported by experimental evidence (6). After peripheral nerve injury, axon degeneration and myelin destruction proceed rapidly. The degenerating nerve is infiltrated by blood-derived macrophages that are responsible for clearing axonal and myelin debris (4,7,8). It has been proposed that most of the cholesterol, and possibly other key lipids released by degenerating axons and myelin, accumulate within Schwann cells and macrophages that remain in the area of degeneration. The salvaged cholesterol appears to be reutilized by the regenerating myelin membranes (4, 9, 10) and by neurons for axonal membrane regeneration. However, direct evidence for the reutilization of cholesterol by axons has not been provided.After nerve injury, synthesis of several proteins is induced in the distal, but not the proximal, segment of the injured nerve (11). One protein in particular, apoE, is produced by infiltrating macrophages and accumulates to levels 100 -200-fold greater than in uninjured nerve (12-15). Synthesis of apoE in neurons per se has not been detected.2 It has been proposed that apoE, together with apoA-I, which enters the nerve from the circulation, play a central role in the reutilization of cholesterol (6,16,17). Current evidence suggests that cholesterol from the cellular and myelin debris is first stored in endoneurial macrophages and is subsequently secreted by the macrophages to form cholesterol-rich, apoE/A-I-containing li...

show abstract

Abnormalities in cholesterol metabolism cause peripheral neuropathy and dementia in AIDS—A hypothesis

Cited by 11 publications

References 52 publications

The macrophage: the intersection between HIV infection and atherosclerosis

The macrophage: the intersection between HIV infection and atherosclerosis

Nerve Regeneration and Cholesterol Reutilization Occur in the Absence of Apolipoproteins E and A‐I in Mice

Role of Lipoproteins in the Delivery of Lipids to Axons during Axonal Regeneration

Contact Info

Product

Resources

About