Alterations in lipid metabolism of spinal cord linked to amyotrophic lateral sclerosis.
Adriano B. Chaves-Filho,Isabella Fernanda Dantas Pinto,Lucas S. Dantas,André Machado Xavier,Alex Inague,Rodrigo Lucas Faria,Marisa Helena Gennari de Medeiros,Isaias Glezer,Marcos Yukio Yoshinaga,Sayuri Miyamoto +9 more
TLDR
A hypothetical model based on neuroprotection of polyunsaturated fatty acids into lipid droplets in response to increased oxidative stress is postulated, suggesting abnormal mitochondria in motor neurons and lipid droplet accumulation in aberrant astrocytes.Abstract:
Amyotrophic lateral sclerosis (ALS) is characterized by progressive loss of upper and lower motor neurons leading to muscle paralysis and death. While a link between dysregulated lipid metabolism and ALS has been proposed, lipidome alterations involved in disease progression are still understudied. Using a rodent model of ALS overexpressing mutant human Cu/Zn-superoxide dismutase gene (SOD1-G93A), we performed a comparative lipidomic analysis in motor cortex and spinal cord tissues of SOD1-G93A and WT rats at asymptomatic (~70 days) and symptomatic stages (~120 days). Interestingly, lipidome alterations in motor cortex were mostly related to age than ALS. In contrast, drastic changes were observed in spinal cord of SOD1-G93A 120d group, including decreased levels of cardiolipin and a 6-fold increase in several cholesteryl esters linked to polyunsaturated fatty acids. Consistent with previous studies, our findings suggest abnormal mitochondria in motor neurons and lipid droplets accumulation in aberrant astrocytes. Although the mechanism leading to cholesteryl esters accumulation remains to be established, we postulate a hypothetical model based on neuroprotection of polyunsaturated fatty acids into lipid droplets in response to increased oxidative stress. Implicated in the pathology of other neurodegenerative diseases, cholesteryl esters appear as attractive targets for further investigations.read more
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Cardiolipin, Mitochondria, and Neurological Disease
TL;DR: A review of the role of Cardiolipin (CL) in nervous system physiology and monogenic and neurodegenerative disease pathophysiology, in addition to its potential application as a biomarker and pharmacological target is presented in this article.
Journal ArticleDOI
Lipid droplets in the nervous system.
TL;DR: The authors reviewed the basic mechanisms of lipid droplet formation, turnover, and function and discussed how these mechanisms enable lipid droplets to function in different cell types of the nervous system under healthy and pathological conditions.
Journal ArticleDOI
Untargeted metabolomics yields insight into ALS disease mechanisms
Stephen A. Goutman,Jonathan Boss,Kai Guo,Fadhl M. Al-Akwaa,Adam Patterson,Sehee Kim,Masha G. Savelieff,Junguk Hur,Eva L. Feldman +8 more
TL;DR: In this analysis, ALS led to significant metabolic pathway alterations, which had correlations to known ALS pathomechanisms in the basic and clinical literature, and may represent important targets for future ALS therapeutics.
Journal ArticleDOI
Astrocytes with TDP-43 inclusions exhibit reduced noradrenergic cAMP and Ca 2+ signaling and dysregulated cell metabolism.
Jelena Velebit,Anemari Horvat,Tina Smolič,Sonja Prpar Mihevc,Boris Rogelj,Robert Zorec,Nina Vardjan +6 more
TL;DR: While in astrocytes with TDP-43 inclusions noradrenergic signaling is reduced, aerobic glycolysis and lipid droplet accumulation are facilitated, suggesting dysregulated astroglial metabolism and metabolic support of neurons in T DP-43-associated ALS and FTD.
Journal ArticleDOI
Diet, Microbiota and Brain Health: Unraveling the Network Intersecting Metabolism and Neurodegeneration.
TL;DR: A comprehensive review of the impact of metabolism, diet and microbiota in neurodegeneration, by affecting simultaneously several aspects of health regarding energy metabolism, immune system and neuronal function is presented.
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