scholarly journals Fatty Acid Binding Protein: Localization and Functional Significance in the Brain

2008 ◽  
Vol 214 (3) ◽  
pp. 213-220 ◽  
Author(s):  
Yuji Owada
Keyword(s):  
Fatty Acid ◽  
Functional Significance ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Protein Localization ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
The Brain

ChemInform Abstract: Role of Heart-Type Fatty Acid Binding Protein in the Brain Function

ChemInform ◽  
2009 ◽  
Vol 40 (26) ◽  
Author(s):  
Keiju Motohashi ◽  
Yui Yamamoto ◽  
Norifumi Shioda ◽  
Hisatake Kondo ◽  
Yuji Owada ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Brain Function ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
The Brain

scholarly journals Fatty Acid Binding Protein 3 Enhances the Spreading and Toxicity of α-Synuclein in Mouse Brain

2020 ◽  
Vol 21 (6) ◽  
pp. 2230 ◽  
Author(s):  
Yasushi Yabuki ◽  
Kazuya Matsuo ◽  
Ichiro Kawahata ◽  
Naoya Fukui ◽  
Tomohiro Mizobata ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Mouse Brain ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Lewy Bodies ◽  
Substantia Nigra Pars Compacta ◽  
Fatty Acid Binding ◽  
Knock Out ◽  
Acid Binding Protein ◽  
The Brain

Oligomerization and/or aggregation of α-synuclein (α-Syn) triggers α-synucleinopathies such as Parkinson’s disease and dementia with Lewy bodies. It is known that α-Syn can spread in the brain like prions; however, the mechanism remains unclear. We demonstrated that fatty acid binding protein 3 (FABP3) promotes propagation of α-Syn in mouse brain. Animals were injected with mouse or human α-Syn pre-formed fibrils (PFF) into the bilateral substantia nigra pars compacta (SNpc). Two weeks after injection of mouse α-Syn PFF, wild-type (WT) mice exhibited motor and cognitive deficits, whereas FABP3 knock-out (Fabp3−/−) mice did not. The number of phosphorylated α-Syn (Ser-129)-positive cells was significantly decreased in Fabp3−/− mouse brain compared to that in WT mice. The SNpc was unilaterally infected with AAV-GFP/FABP3 in Fabp3−/− mice to confirm the involvement of FABP3 in the development of α-Syn PFF toxicity. The number of tyrosine hydroxylase (TH)- and phosphorylated α-Syn (Ser-129)-positive cells following α-Syn PFF injection significantly decreased in Fabp3−/− mice and markedly increased by AAV-GFP/FABP3 infection. Finally, we confirmed that the novel FABP3 inhibitor MF1 significantly antagonized motor and cognitive impairments by preventing α-Syn spreading following α-Syn PFF injection. Overall, FABP3 enhances α-Syn spreading in the brain following α-Syn PFF injection, and the FABP3 ligand MF1 represents an attractive therapeutic candidate for α-synucleinopathy.

scholarly journals Regulation of Dopaminergic Neuronal Activity by Heart-type Fatty Acid Binding Protein in the Brain

2011 ◽  
Vol 131 (4) ◽  
pp. 497-501 ◽  
Author(s):  
Yui YAMAMOTO ◽  
Norifumi SHIODA ◽  
Yuji OWADA ◽  
Kohji FUKUNAGA
Keyword(s):  
Fatty Acid ◽  
Neuronal Activity ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
The Brain

scholarly journals ApoE4 disrupts interaction of sortilin with fatty acid-binding protein 7 essential to promote lipid signaling

2021 ◽  
Author(s):  
Antonino Asaro ◽  
Rishabhdev Sinha ◽  
Magda Bakun ◽  
Oleksandra Kalnytska ◽  
Anne-Sophie Carlo-Spiewok ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Mechanistic Explanation ◽  
Functional Expression ◽  
Neuronal Uptake ◽  
Lipid Signaling ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
The Brain

Sortilin is a receptor for neuronal uptake of apolipoprotein E. Sortilin-dependent uptake of lipidated apoE promotes conversion of polyunsaturated fatty acids (PUFA) into neuromodulators that induce anti-inflammatory gene expression in the brain. This neuroprotective pathway works with apoE3 but is lost with apoE4, the main risk factor for Alzheimer disease (AD). Here, we elucidated steps in cellular handling of lipids through sortilin, and why they are disrupted by apoE4. Combining unbiased proteome screens with analyses in mouse models, we uncover interaction of sortilin with fatty acid-binding protein (FABP) 7, the intracellular carrier for PUFA in the brain. In the presence of apoE3, sortilin promotes functional expression of FABP7 and its ability to elicit lipid-dependent gene transcription. By contrast, apoE4 binding blocks sortilin sorting, causing catabolism of FABP7 and impairing lipid signaling. Reduced FABP7 levels in the brain of AD patients expressing apoE4 substantiate the relevance of these interactions for neuronal lipid homeostasis. Taken together, we document interaction of sortilin with mediators of extracellular and intracellular lipid transport that provides a mechanistic explanation for loss of a neuroprotective lipid metabolism in AD.

scholarly journals Fatty Acid-Binding Protein 3 Expression in the Brain and Skin in Human Synucleinopathies

2021 ◽  
Vol 13 ◽  
Author(s):  
Hideki Oizumi ◽  
Kenshi Yamasaki ◽  
Hiroyoshi Suzuki ◽  
Takafumi Hasegawa ◽  
Yoko Sugimura ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Dopaminergic Neurons ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Amyloid Β ◽  
Human Tissues ◽  
Adult Onset ◽  
Fatty Acid Binding ◽  
Acid Binding Protein ◽  
The Brain

Parkinson’s disease (PD) and multiple system atrophy are types of adult-onset neurodegenerative disorders named synucleinopathies, which are characterized by prominent intracellular α-synuclein (αSyn) aggregates. We have previously found that αSyn aggregates and the vulnerability of dopaminergic neurons in the mouse brain are partly associated with the expression of fatty acid-binding protein 3 (FABP3, heart FABP). However, it remains to be elucidated whether FABP3 accumulation is associated with αSyn aggregates in human tissues. Here, we histologically studied FABP3 expression in human tissues obtained from patients with synucleinopathies, patients with Alzheimer disease (AD) and controls. We found that (1) a variety of neurons expressed the FABP3 protein in human brain tissues, (2) FABP3 was colocalized with αSyn aggregates in the brains of individuals with synucleinopathies but not with amyloid β or p-tau aggregates in the brains of individuals with AD, and (3) FABP3 was not present in p-αSyn deposits in biopsied skin tissues from individuals with PD. These findings suggest that FABP3 expression is associated with αSyn aggregation in synucleinopathies and provide new insights into the involvement of FABP3 in synucleinopathies.

scholarly journals ApoE4 disrupts interaction of sortilin with fatty acid-binding protein 7 essential to promote lipid signaling

2021 ◽  
Author(s):  
Antonino Asaro ◽  
Rishabhdev Sinha ◽  
Magda Bakun ◽  
Oleksandra Kalnytska ◽  
Anne-Sophie Carlo-Spiewok ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Mechanistic Explanation ◽  
Functional Expression ◽  
Lipid Signaling ◽  
Fatty Acid Binding ◽  
Inflammatory Gene Expression ◽  
Acid Binding Protein ◽  
The Brain

Sortilin is a neuronal receptor for apolipoprotein E. Sortilin-dependent uptake of lipidated apoE promotes conversion of polyunsaturated fatty acids (PUFA) into neuromodulators that induce anti-inflammatory gene expression in the brain. This neuroprotective pathway works with apoE3 but is lost with apoE4, the main risk factor for Alzheimer's disease (AD). Here, we elucidated steps in cellular handling of lipids through sortilin, and why they are disrupted by apoE4. Combining unbiased proteome screens with analyses in mouse models, we uncover interaction of sortilin with fatty acid-binding protein (FABP) 7, the intracellular carrier for PUFA in the brain. In the presence of apoE3, sortilin promotes functional expression of FABP7 and its ability to elicit lipid-dependent gene transcription. By contrast, apoE4 binding blocks sortilin sorting, causing catabolism of FABP7 and impairing lipid signaling. Reduced FABP7 levels in the brain of AD patients expressing apoE4 substantiate the relevance of these interactions for neuronal lipid homeostasis. Taken together, we document interaction of sortilin with mediators of extracellular and intracellular lipid transport that provides a mechanistic explanation for loss of a neuroprotective lipid metabolism in AD.

scholarly journals Purification and characterization of the human epidermal fatty acid-binding protein: localization during epidermal cell differentiation in vivo and in vitro

1994 ◽  
Vol 302 (2) ◽  
pp. 363-371 ◽  
Author(s):  
G Siegenthaler ◽  
R Hotz ◽  
D Chatellard-Gruaz ◽  
L Didierjean ◽  
U Hellman ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Human Skin ◽  
Fatty Acid Binding Protein ◽  
Binding Protein ◽  
Protein Localization ◽  
Keratinocyte Differentiation ◽  
Psoriatic Skin ◽  
Skin Lipid ◽  
Fatty Acid Binding ◽  
Acid Binding Protein

Epidermal fatty acid-binding protein (E-FABP) was isolated from human skin and purified to homogeneity. Its molecular mass was estimated to be 15 kDa and the pI of non-denaturing protein was 5.6. Scatchard-plot analysis revealed one class of binding site for oleic acid with a Kd of 0.46 microM. Structure-binding relation experiments revealed a high affinity of E-FABP for stearic acid which decreased on reduction of the number of carbon atoms or introduction of double bonds into the fatty acid chain. Squalene, cholesterol and retinoic acid isomers showed no affinity, suggesting that E-FABP displays high specificity for fatty acids. E-FABP is a scarce cytosolic protein (0.065% of total protein). Only trace amounts could be detected in normal human skin but up to 42.5 +/- 3.4 pmol/mg of protein was found in a non-malignant defect of keratinocyte differentiation (psoriatic lesions). E-FABP levels were low in cultured human keratinocytes grown under proliferation-stimulating conditions but increased about 2-fold on induction of differentiation by Ca2+. Immunohistochemical localization showed cytosolic staining in differentiated cells of normal and psoriatic skin, suggesting a link between E-FABP and keratinocyte differentiation. The presence of E-FABP in tissues other than skin (heart, intestine and adipose tissue) excludes its specific role in fatty acid metabolism in epithelial cells or its involvement in skin lipid-barrier function.

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