Effect of conjugated linoleic acid, μ-calpain inhibitor, on pathogenesis of Alzheimer's disease

Lee, Eun-Young; Eom, Ji Eun; Kim, Hye Lin; Baek, Kyung Hye; Jun, Kyu Yeon; Kim, Hwa Jung; Lee, Minyung; Mook‐Jung, Inhee; Kwon, Young Joo

doi:10.1016/j.bbalip.2012.12.003

Cited by 44 publications

(21 citation statements)

References 61 publications

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“…Changes in calcium homeostasis are consistent with changes in mitochondrial regulatory pathways and support observations that mice harboring presenilin 1 mutations, an established cause of familial AD (FAD), display mitochondrial dysfunction and altered cytosolic calcium homeostasis [112]. Such observations also provide evidence for mitochondria as an upstream affecter in the production of β-amyloid since altered amyloid processing has been correlated with altered calcium homeostasis [113]. Although there are conflicting accounts as to whether β-amyloid itself induces or alters the calcium changes observed in AD [114], cybrid studies provide insight into mechanisms that may nurture β-amyloid production prior to its potential effects on intracellular calcium.…”

Section: Mitochondria and Iron In Sporadic Alzheimer’s Diseasesupporting

confidence: 73%

Common defects of mitochondria and iron in neurodegeneration and diabetes (MIND): A paradigm worth exploring

Stroh¹,

Swerdlow²,

Zhu³

2014

Biochemical Pharmacology

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A popular, if not centric, approach to the study of an event is to first consider that of the simplest cause. When dissecting the underlying mechanisms governing idiopathic diseases, this generally takes the form of an ab initio genetic approach. To date, this genetic ‘smoking gun’ has remained elusive in diabetes mellitus and for many affected by neurodegenerative diseases. With no single gene, or even subset of genes, conclusively causative in all cases, other approaches to the etiology and treatment of these diseases seem reasonable, including the correlation of a systems’ predisposed sensitivity to particular influence. In the cases of diabetes mellitus and neurodegenerative diseases, overlapping themes of mitochondrial influence or dysfunction and iron dyshomeostasis are apparent and relatively consistent. This mini-review discusses the influence of mitochondrial function and iron homeostasis on diabetes mellitus and neurodegenerative disease, namely Alzheimer’s disease. Also discussed is the incidence of diabetes accompanied by neuropathy and neurodegeneration along with neurodegenerative disorders prone to development of diabetes. Mouse models containing multiple facets of this overlap are also described alongside current molecular trends attributed to both diseases. As a way of approaching the idiopathic and complex nature of these diseases we are proposing the consideration of a MIND (mitochondria, iron, neurodegeneration, and diabetes) paradigm in which systemic metabolic influence, iron homeostasis, and respective genetic backgrounds play a central role in the development of disease.

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Section: Mitochondria and Iron In Sporadic Alzheimer’s Diseasesupporting

confidence: 73%

Common defects of mitochondria and iron in neurodegeneration and diabetes (MIND): A paradigm worth exploring

Stroh¹,

Swerdlow²,

Zhu³

2014

Biochemical Pharmacology

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“…The course of these diseases is also a considerable social problem, affecting not only patients but their whole families [2]. Among various mechanisms of neurodegenerative processes, a disrupted neuronal intracellular calcium homeostasis leading to hyper-activation of μ-calpain could be listed at a very beginning [3,4]. Thus, an inhibition of calpain activity became crucial among approaches in the treatment and prevention of neurodegenerative diseases [5].…”

Section: Introductionmentioning

confidence: 99%

Polyelectrolyte-coated nanocapsules containing undecylenic acid: Synthesis, biocompatibility and neuroprotective properties

Piotrowski

Jantas

Szczepanowicz

et al. 2015

Colloids and Surfaces B: Biointerfaces

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“…That CLAs exert effects in brain and affect neuronal function is further supported by the fact that lately, a negative correlation was found between CLA and Alzheimer's disease [42]. In a human neuroblastoma cell line, CLA-isomers decreased tau phosphorylation and showed neuroprotective effects against β-amyloid peptides through a specific inhibition of the calcium-dependent cysteine protease µ-calpain.…”

Section: Discussionmentioning

confidence: 71%

Mice Lacking Free Fatty Acid Receptor 1 (GPR40/FFAR1) are Protected Against Conjugated Linoleic Acid-Induced Fatty Liver but Develop Inflammation and Insulin Resistance in the Brain

Sartorius

Drescher

Panse

et al. 2015

Cell Physiol Biochem

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Background/Aims:Conjugated linoleic acids (CLAs) affect body fat distribution, induce insulin resistance and stimulate insulin secretion. The latter effect is mediated through the free fatty acid receptor-1 (GPR40/FFAR1). This study examines whether GPR40/FFAR1 interacts with tissue specific metabolic changes induced by CLAs. MethodsandResults:After chronic application of CLAs C57BL/6J wild type (WT) and GPR40/FFAR1 (Ffar1^-/-) knockout mice developed insulin resistance. Although CLAs accumulated in liver up to 46-fold genotype-independently, hepatic triglycerides augmented only in WT mice. This triglyceride deposition was not associated with increased inflammation. In contrast, in brain of CLA fed Ffar1^-/- mice mRNA levels of TNF-α were 2-fold higher than in brain of WT mice although CLAs accumulated genotype-independently in brain up to 4-fold. Concomitantly, Ffar1^-/- mice did not respond to intracerebroventricular (i.c.v.) insulin injection with an increase in cortical activity while WT mice reacted as assessed by radiotelemetric electrocorticography (ECoG) measurements. In vitro incubation of primary murine astrocytes confirmed that CLAs stimulate neuronal inflammation independent of GPR40/FFAR1. Conclusion:This study discloses that GPR40/FFAR1 indirectly modulates organ-specific effects of CLAs: the expression of functional GPR40/FFAR1 counteracts CLA-induced inflammation and insulin resistance in the brain, but favors the development of fatty liver.

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Effect of conjugated linoleic acid, μ-calpain inhibitor, on pathogenesis of Alzheimer's disease

Cited by 44 publications

References 61 publications

Common defects of mitochondria and iron in neurodegeneration and diabetes (MIND): A paradigm worth exploring

Common defects of mitochondria and iron in neurodegeneration and diabetes (MIND): A paradigm worth exploring

Polyelectrolyte-coated nanocapsules containing undecylenic acid: Synthesis, biocompatibility and neuroprotective properties

Mice Lacking Free Fatty Acid Receptor 1 (GPR40/FFAR1) are Protected Against Conjugated Linoleic Acid-Induced Fatty Liver but Develop Inflammation and Insulin Resistance in the Brain

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