Lovastatin Differentially Affects Neuronal Cholesterol and Amyloid-β Production in vivo and in vitro.

CONCLUSIONS: Lovastatin modifies the mevalonate pathway without affecting cholesterol levels in vivo and is able to reduce Aβ levels only in vitro. PMID: 26096465 [PubMed - as supplied by publisher]
Source: CNS Neuroscience and Therapeutics - Category: Neuroscience Authors: Tags: CNS Neurosci Ther Source Type: research

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Source: BMJ Comments - Category: General Medicine Source Type: forums
Publication date: Available online 17 September 2019Source: Molecular and Cellular EndocrinologyAuthor(s): C. Fraichard, F. Bonnet, A. Garnier, M. Hébert-Schuster, A. Bouzerara, P. Gerbaud, I. Ferecatu, T. Fournier, I. Hernandez, S. Trabado, J. GuibourdencheAbstractPlacental syncytiotrophoblast (ST) is considered as the main placental endocrine tissue secreting progesterone, a steroid essential for maintenance of pregnancy. However, each step of progestins production has been poorly investigated in villous cytotrophoblast (VCT) regarding ST formation. We aimed to characterize progestins production during human diffe...
Source: Molecular and Cellular Endocrinology - Category: Endocrinology Source Type: research
CONCLUSIONS Silencing ACAT1 attenuates Aβ₂₅₋₃₅-induced cytotoxicity and cell apoptosis in SH-SY5Y cells, which may due to the synergistic effect of ACAT1 and COX2 through PKC/ERK pathways. PMID: 30541014 [PubMed - in process]
Source: Medical Science Monitor - Category: Research Tags: Med Sci Monit Source Type: research
Publication date: July 2018Source: Redox Biology, Volume 17Author(s): Gabriella Testa, Erica Staurenghi, Serena Giannelli, Simona Gargiulo, Michela Guglielmotto, Massimo Tabaton, Elena Tamagno, Paola Gamba, Gabriella LeonarduzziAbstractIt is now established that cholesterol oxidation products (oxysterols) are involved in several events underlying Alzheimer's disease (AD) pathogenesis. Of note, certain oxysterols cause neuron dysfunction and degeneration but, recently, some of them have been shown also to have neuroprotective effects. The present study, which aimed to understand the potential effects of 24-hydroxycholestero...
Source: Redox Biology - Category: Biology Source Type: research
The β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) initiates the production of amyloid-β peptide (Aβ), which is central to the pathogenesis of Alzheimer's disease (AD). Changes in brain cholesterol homeostasis have been suggested to affect Aβ metabolism. Cholesterol homeostasis is maintained in the brain by apolipoprotein E (apoE). The apoE4 isoform constitutes the major risk factor for AD. Here, we investigated the effect of apoE forms on Aβ generation and on BACE1 levels. We also examined the potential involvement in these processes of cholesterol transporters ABCG1 and ABCG4 or the l...
Source: Biochemical Journal - Category: Biochemistry Authors: Tags: Research Articles Source Type: research
Conclusions: In the cell cultures, we observed that seladin-1 protein levels increased after aromatase enzyme inhibition. The hippocampal aromatase protein levels decreased following chronic seladin-1 inhibition in icv inhibitor-administered rats; however, the aromatase levels in the dentate gyrus of seladin-1 knockout (SelKO) AD male mice increased. These findings indicate a partial relationship between these proteins and their roles in AD pathology.Pharmacology 2018;102:42 –52
Source: Pharmacology - Category: Drugs & Pharmacology Source Type: research
ApoE isoforms and carboxyl-terminal truncated apoE4 forms affect neuronal BACE1 levels and Aβ production independently of their cholesterol efflux capacity. Biochem J. 2018 May 09;: Authors: Dafnis I, Raftopoulou C, Mountaki C, Megalou E, Zannis VI, Chroni A Abstract The beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) initiates the production of amyloid-beta peptide (Aβ) which is central to the pathogenesis of Alzheimer's disease (AD). Changes in brain cholesterol homeostasis have been suggested to affect Aβ metabolism. Cholesterol homeostasis is maintained in the brain by...
Source: The Biochemical Journal - Category: Biochemistry Authors: Tags: Biochem J Source Type: research
In this study, we investigated possible relationships among insulin signaling and cholesterol biosynthesis, along with the effects of Aβ 42 on these pathways in vitro . We found that neuroblastoma 2a (N2a) cells transfected with the human gene encoding amyloid- β protein precursor (AβPP) (N2a-AβPP) produced Aβ and exhibited insulin resistance by reduced p-Akt and a suppressed cholesterol-synthesis pathway following insulin treatment, and by increased phosphorylation of insulin receptor subunit-1 at serine 612 (p-IRS-S612) as compared to parental N2a ce lls. Treatment of human neuroblastoma SH-SY5Y...
Source: Neuroscience Bulletin - Category: Neuroscience Source Type: research
Abstract Patients with Alzheimer's disease (AD) display amyloidopathy and tauopathy. In mouse models of AD, pharmacological inhibition using small molecule enzyme inhibitors or genetic inactivation of acyl-coenzyme A (Acyl-CoA):cholesterol acyltransferase 1 (ACAT1) diminished amyloidopathy and restored cognitive deficits. In microglia, ACAT1 blockage increases autophagosome formation and stimulates amyloid β peptide1-42 degradation. Here, we hypothesize that in neurons ACAT1 blockage augments autophagy and increases autophagy-mediated degradation of P301L-tau protein. We tested this possibility in murine neur...
Source: Neurobiology of Aging - Category: Geriatrics Authors: Tags: Neurobiol Aging Source Type: research
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