Alpha-synuclein elicits glucose uptake and utilization in adipocytes through the Gab1/PI3K/Akt transduction pathway

Rodriguez-Araujo, Gerardo; Nakagami, Hironori; Hayashi, Hiroki; Mori, Masaki; Shiuchi, Tetsuya; Minokoshi, Yasuhiko; Nakaoka, Yoshikazu; Takami, Yoichi; Komuro, Issei; Morishita, Ryuichi; Kaneda, Yasufumi

doi:10.1007/s00018-012-1198-8

Cited by 42 publications

(37 citation statements)

References 41 publications

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“…[29] It seems that α-syn can facilitate the entrance of glucose into adipose tissues and skeletal muscle through a G-protein-coupled receptor known as LPAR2-CD90. [30]…”

Section: Alpha-synuclein Functionsmentioning

confidence: 99%

Alpha-synuclein structure, functions, and interactions

Emamzadeh¹

2016

J Res Med Sci

213

173

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At present, when a clinical diagnosis of Parkinson's disease (PD) is made, serious damage has already been done to nerve cells of the substantia nigra pars compacta. The diagnosis of PD in its earlier stages, before this irreversible damage, would be of enormous benefit for future treatment strategies designed to slow or halt the progression of this disease that possibly prevents accumulation of toxic aggregates. As a molecular biomarker for the detection of PD in its earlier stages, alpha-synuclein (α-syn), which is a key component of Lewy bodies, in which it is found in an aggregated and fibrillar form, has attracted considerable attention. Here, α-syn is reviewed in details.

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“…[29] It seems that α-syn can facilitate the entrance of glucose into adipose tissues and skeletal muscle through a G-protein-coupled receptor known as LPAR2-CD90. [30]…”

Section: Alpha-synuclein Functionsmentioning

confidence: 99%

Alpha-synuclein structure, functions, and interactions

Emamzadeh¹

2016

J Res Med Sci

213

173

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“…In contrast, α-synuclein ablation exacerbates insulin resistance in mouse adipose tissue and skeletal muscle, as well as in patients with low α-synuclein blood levels and increased insulin resistance [201]. In the adipose tissue and skeletal muscle of α-synuclein knockout mice, it has also been observed an increase in GLUT4-driven glucose uptake through an insulin-independent mechanism [202]. …”

Section: Metabolic Disturbances In Genetic Models Of Pdmentioning

confidence: 99%

Mitochondrial control of cell bioenergetics in Parkinson’s disease

Requejo-Aguilar

Bolaños

2016

Free Radical Biology and Medicine

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Parkinson disease (PD) is a neurodegenerative disorder characterized by a selective loss of dopaminergic neurons in the substantia nigra. The earliest biochemical signs of the disease involve failure in mitochondrial-endoplasmic reticulum cross talk and lysosomal function, mitochondrial electron chain impairment, mitochondrial dynamics alterations, and calcium and iron homeostasis abnormalities. These changes are associated with increased mitochondrial reactive oxygen species (mROS) and energy deficiency. Recently, it has been reported that, as an attempt to compensate for the mitochondrial dysfunction, neurons invoke glycolysis as a low-efficient mode of energy production in models of PD. Here, we review how mitochondria orchestrate the maintenance of cellular energetic status in PD, with special focus on the switch from oxidative phosphorylation to glycolysis, as well as the implication of endoplasmic reticulum and lysosomes in the control of bioenergetics.

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“…These aggregates are known to form as a result of three distinct point mutations [5-7], or from overexpression of αS [8, 9]. A clear physiological role for αS within cells has not been uniquely identified [10]; however, αS has been shown to localize to nerve termini [11-13], bind copper [14], and play a role in the uptake and release of neurotransmitters from vesicles [1, 2, 15-18], as well as in the regulation of glucose uptake [19]. αS has also been shown to interact with proteins involved in lipid metabolism [20, 21], and binds to negatively charged lipids [22].…”

Section: Introductionmentioning

confidence: 99%

Conformational heterogeneity of α -synuclein in membrane

Vermaas

Tajkhorshid

2014

Biochimica et Biophysica Acta (BBA) - Biomembranes

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α-Synuclein (αS) is a natively disordered protein in solution, thought to be involved in the fusion of neurotransmitter vesicles to cellular membranes during neurotransmission. Monomeric αS has been previously characterized in two distinct membrane–associated conformations: a broken-helix structure, and an extended helix. Employing atomistic molecular dynamics and a novel membrane representation with significantly enhanced lipid mobility (HMMM), we investigate the process of spontaneous membrane binding of αS and the conformational dynamics of monomeric αS in its membrane-bound form. By repeatedly placing helical αS monomers in solution above a planar lipid bilayer and observing their spontaneous association and insertion into the membrane during twenty independent unbiased simulations, we are able to characterize αS in its membrane-bound state, suggesting that αS has a highly variable membrane insertion depth at equilibrium. Our simulations also capture two distinct states of αS, the starting broken-helix conformation seen in the micelle bound NMR structures, and a semi-extended helix. Analysis of lipid distributions near αS monomers indicates that the transition to a semi-extended helix is facilitated by concentration of phosphatidyl-serine headgroups along the inner edge of the protein. Such a lipid-mediated transition between helix-turn-helix and extended conformations of αS may also occur in vivo, and may be important for the physiological function of αS.

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Alpha-synuclein elicits glucose uptake and utilization in adipocytes through the Gab1/PI3K/Akt transduction pathway

Cited by 42 publications

References 41 publications

Alpha-synuclein structure, functions, and interactions

Alpha-synuclein structure, functions, and interactions

Mitochondrial control of cell bioenergetics in Parkinson’s disease

Conformational heterogeneity of α -synuclein in membrane

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