Linking lipids to Alzheimer's disease: cholesterol and beyond
Gilbert Di Paolo,Tae-Wan Kim +1 more
TLDR
Exploration of lipid dysregulation in AD and identification of novel therapeutic agents acting through relevant lipid pathways offers new and effective options for the treatment of this devastating disorder.Abstract:
Lipid-mediated signalling regulates a plethora of physiological processes, including crucial aspects of brain function. In addition, dysregulation of lipid pathways has been implicated in a growing number of neurodegenerative disorders, such as Alzheimer's disease (AD). Although much attention has been given to the link between cholesterol and AD pathogenesis, growing evidence suggests that other lipids, such as phosphoinositides and phosphatidic acid, have an important role. Regulators of lipid metabolism (for example, statins) are a highly successful class of marketed drugs, and exploration of lipid dysregulation in AD and identification of novel therapeutic agents acting through relevant lipid pathways offers new and effective options for the treatment of this devastating disorder.read more
Citations
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Polyunsaturated fatty acids and their metabolites in brain function and disease
Richard P. Bazinet,Sophie Layé +1 more
TL;DR: Diet and drugs targeting PUFAs may lead to novel therapeutic approaches for the prevention and treatment of brain disorders, including Alzheimer's disease and major depression.
Journal ArticleDOI
On the Mechanism of Cytoprotection by Ferrostatin-1 and Liproxstatin-1 and the Role of Lipid Peroxidation in Ferroptotic Cell Death.
Omkar Zilka,Ron Shah,Bo Li,José Pedro Friedmann Angeli,Markus Griesser,Marcus Conrad,Derek A. Pratt +6 more
TL;DR: It is demonstrated that potent RTAs subvert ferroptosis and suggest that lipid peroxidation (autoxidation) may play a central role in the process.
Journal ArticleDOI
Comparative lipidomic analysis of mouse and human brain with Alzheimer disease.
Robin B. Chan,Tiago Gil Oliveira,Etty Cortes,Lawrence S. Honig,Karen Duff,Scott A. Small,Markus R. Wenk,Guanghou Shui,Gilbert Di Paolo +8 more
TL;DR: In this paper, a system-based approach was employed to determine the lipidome of brain tissues affected by Alzheimer disease using liquid chromatography-mass spectrometry to profile extracts from the prefrontal cortex, entorhinal cortex, and cerebellum of late-onset AD patients.
Journal ArticleDOI
Genetics of Alzheimer’s Disease
TL;DR: The known genetics of early- and late-onset Alzheimer's disease are reviewed, including APOE, which is a complex disorder with environmental and genetic components leading to disease.
Journal ArticleDOI
TREM2 Is a Receptor for β-Amyloid that Mediates Microglial Function
Yingjun Zhao,Xi-Lin Wu,Xiaoguang Li,Lu Lin Jiang,Xun Gui,Yan Liu,Yu Sun,Bing Zhu,Juan C. Piña-Crespo,Muxian Zhang,Ningyan Zhang,Xiaochun Chen,Guojun Bu,Zhiqiang An,Timothy Y. Huang,Huaxi Xu,Huaxi Xu +16 more
TL;DR: TREM2 is demonstrated as a microglial Aβ receptor transducing physiological and AD-related pathological effects associated with Aβ, and TREM2 interaction with its signaling adaptor DAP12 is enhanced by A β, regulating downstream phosphorylation of SYK and GSK3β.
References
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TL;DR: A two-stage genome-wide association study of Alzheimer's disease involving over 16,000 individuals, the most powerful AD GWAS to date, produced compelling evidence for association with Alzheimer's Disease in the combined dataset.