Alzheimer's disease: Cholesterol a menace?

Mathew, Anila; Yoshida, Yasuhiko; Maekawa, Toru; Kumar, D. Sakthi

doi:10.1016/j.brainresbull.2011.06.006

Cited by 34 publications

(34 citation statements)

References 166 publications

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“…Accumulation of neurotoxic Aβ peptide in the brain acts as the most important pathogenic marker contributing to neurodegeneration [37,38]. The levels of Aβ in the brain are controlled by its rates of production from the larger Aβ-precursor protein and the rates of clearance [14,39].…”

Section: Discussionmentioning

confidence: 99%

Clearance of Amyloid Beta Plaques from Brain of Alzheimeric Rats by Lavandula angustifolia

Soheili¹,

Tavirani²,

Saifeddine³

2012

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An important marker in neurodegenerative Alzheimer's disease (AD) is abnormal production of amyloid beta (Aβ) peptide leading to formation of plaques in the brain. Through decreasing Aβ aggregates, anti-inflammatory agents, phagocytosis, and proteolytic enzymes are known to decline risk of Aβ plaque formation. In the previous study we showed that aqueous extract of Lavandula angustifolia (lavender), with known anti-inflammatory effects, improves memory deficits in animal model of Alzheimer. Here, we assess if lavender play a role in clearance of Aβ plaques in the hippocampus. The Alzheimeric animals were created with intracerebroventricular injection of Aβ 1-42. To confirm formation of Aβ plaques, brain sections were stained by Congo red method. Twenty days post-injection they were administered with different doses (50, 100 and 200 mg/kg) of the aqueous extract of lavender for duration of 20 days. Our results demonstrated that 50 mg/kg of lavender not effectively influenced the Aβ plaques. On the other hand, the herbal medicine at the doses of 100 and 200 mg/kg markedly decreased the extent of Aβ aggregates. We concluded that the lavender extract dose dependently underlies elimination of Aβ plaques. The exact mechanism by which the herbal medicine removes the Aβ aggregates needs to be elucidated.

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Section: Discussionmentioning

confidence: 99%

Clearance of Amyloid Beta Plaques from Brain of Alzheimeric Rats by Lavandula angustifolia

Soheili¹,

Tavirani²,

Saifeddine³

2012

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“…13,623 As advocated by the freeradical theory of aging, 468,624,625 slower metabolic rate, for example, induced by moderate hypoxia, 626 enhances life span by producing less radical oxidative damage from mitochondrial activity, whereas hyperoxic conditions shorten life span of cultured cells. 627 Evidence for the association between mitochondrial ROS and aging was obtained from longevity observed in mice overexpressing mitochondrial catalase.…”

Section: Metabolism Aging Diabetes Andmentioning

confidence: 99%

Bioinorganic Chemistry of Alzheimer’s Disease

2012

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“…Cholesterol (CH), its precursors and oxysterols have been consistently implicated in brain aging and neurodegeneration [2,[13][14][15]. The mechanisms underlying this relationship, however, remain ill-defined.…”

Section: Brain Sterols/oxysterolsmentioning

confidence: 99%

“…It is estimated that by the year 2050 the number of patients living with AD in the US may rise to 13-16 million while the worldwide prevalence could reach a staggering 1 in 85 or 75-100 million cases [2][3][4][5]. Pathological hallmarks of AD include extracellular deposits of β-amyloid (plaques), neurites containing hyperphosphorylated tau (neurofibrillary tangles) and loss of neurons in discrete regions of the basal forebrain, hippocampus and association cortices [6][7][8][9][10][11].…”

Section: Admentioning

confidence: 99%

HemeOxygenase-1: Transducer of Sterol Dys-Regulation in Alzheimer Disease

HM¹

2014

J Glycomics Lipidomics

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ADAD is a progressive, degenerative, dementing disorder and the sixth leading cause of the death in the US [1]. It is estimated that by the year 2050 the number of patients living with AD in the US may rise to 13-16 million while the worldwide prevalence could reach a staggering 1 in 85 or 75-100 million cases [2][3][4][5]. Pathological hallmarks of AD include extracellular deposits of β-amyloid (plaques), neurites containing hyperphosphorylated tau (neurofibrillary tangles) and loss of neurons in discrete regions of the basal forebrain, hippocampus and association cortices [6][7][8][9][10][11]. A largely overlooked pathological feature of AD, originally described over a century ago by Alois Alzheimer, is the accumulation of "adipose inclusions" or "lipoid granules" suggesting aberrant lipid homeostasis in this degenerative state [12]. Although medications (cholinesterase inhibitors) capable of conferring transient symptomatic relief are available for the management of AD, there is currently no disease-modifying intervention which unequivocally slows arrests or reverses the degenerative process. Brain Sterols/OxysterolsCholesterol (CH), its precursors and oxysterols have been consistently implicated in brain aging and neurodegeneration [2,[13][14][15]. The mechanisms underlying this relationship, however, remain ill-defined. In the CNS, sterols including CH subserves numerous biological functions essential for cell survival and homeostasis [16]. Mammalian CNS development is highly dependent on CH [17]; it is therefore not surprising that altered CH homeostasis occurs in a host of neurological conditions [18,19]. Glial CH can be enzymatically (via CH 7a-, 24-and 25-hydroxylase) or non-enzymatically (via oxidative stress) metabolized to oxysterols. On the one hand, augmented oxysterol concentrations may protect neural tissues by attenuating β-amyloiddeposition and by activation of the liver X receptor (LXR). The latter mediates up-regulation of apolipoprotein E (apoE) which, in turn, promotes glial CH efflux thatfacilitates neuronal membrane repair. However, LXR activation may also inhibit glial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and de novo CH biosynthesis. The latter establishes a negative servomechanism that limits the extent of oxysterol production and CH efflux by these cells. Moreover, primary neuronal cultures have been shown to be highly sensitive to 25-OH cytotoxicity, with lesser vulnerability to other common oxysterols such as 7-keto, 22-OH and 7β-OH [20]. Oxysterols may also promote cytotoxicity in primary astrocytes and apoptosis in microglial cells.Several critical lines of evidence have implicated sterol (dys) regulation and the formation of oxysterols in the pathogenesis of AD. For example, genetic association studies have linkedpolymorphisms ofAPOE, SORL1, CLU andABCA7 genes, which directly or indirectlyimpact lipid homeostasis, with the development of AD [21,22]. In addition, dyslipidemia has been identified in several distinct populations as an important midlife risk factor for s...

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Alzheimer's disease: Cholesterol a menace?

Cited by 34 publications

References 166 publications

Clearance of Amyloid Beta Plaques from Brain of Alzheimeric Rats by Lavandula angustifolia

Clearance of Amyloid Beta Plaques from Brain of Alzheimeric Rats by Lavandula angustifolia

Bioinorganic Chemistry of Alzheimer’s Disease

HemeOxygenase-1: Transducer of Sterol Dys-Regulation in Alzheimer Disease

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