Mode of action of taurine as a neuroprotector

Wu, Heng; Jin, Ying; Wei, Jianning; Ji, Hong; Sha, Di; Wu, Jang‐Yen

doi:10.1016/j.brainres.2005.01.058

Cited by 146 publications

(93 citation statements)

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“…Both mIns and taurine are major osmolytes in the brain (Thurston et al 1989;Pasantes-Morales and Schousboe 1997), and the concurrent higher levels of both metabolites in dorsal hippocampus and frontal cortex could thus well indicate changes in cell volume regulation after the appearance of plaques. Taurine has also been suggested to have several other physiological roles in the brain, such as neuromodulation (Muramatsu et al 1978) and neuroprotection, and it should be noted that taurine protects neurons against both Ab-and glutamate receptor agonist-induced toxicity (Paula-Lima et al 2005;Wu et al 2005). The higher level of taurine in McGill-R-Thy1-APP rats could be related to any of these suggested roles.…”

Section: Myo-inositol Glutamine and Taurinementioning

confidence: 95%

Altered neurochemical profile in the McGill‐R‐Thy1‐APP rat model of Alzheimer's disease: a longitudinal in vivo¹H MRS study

Nilsen

Melø

Sæther

et al. 2012

Journal of Neurochemistry

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We investigated metabolite levels during the progression of pathology in McGill-R-Thy1-APP rats, a transgenic animal model of Alzheimer's disease, and in healthy age-matched controls. Rats were subjected to in vivo 1 H magnetic resonance spectroscopy (MRS) of the dorsal hippocampus at age 3, 9 and 12 months and of frontal cortex at 9 and 12 months. At 3 months, a stage in which only Ab oligomers are present, lower glutamate, myo-inositol and total choline content were apparent in McGill-R-Thy1-APP rats. At age 9 months, lower levels of glutamate, GABA, N-acetylaspartate and total choline and elevated myo-inositol and taurine were found in dorsal hippocampus, whereas lower levels of glutamate, GABA, glutamine and N-acetylaspartate were found in frontal cortex.At age 12 months, only the taurine level was significantly different in dorsal hippocampus, whereas taurine, myo-inositol, N-acetylaspartate and total creatine levels were significantly higher in frontal cortex. McGill-R-Thy1-APP rats did not show the same changes in metabolite levels with age as displayed in the controls, and overall, prominent and complex metabolite differences were evident in this transgenic rat model of Alzheimer's disease. The findings also demonstrate that in vivo 1 H MRS is a powerful tool to investigate diseaserelated metabolite changes in the brain. Keywords: biomarkers, GABA, glutamate, metabolism, N-acetylaspartate, transgenic rats. Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia in the elderly. It is characterized by accumulation of extracellular plaques containing aggregated amyloid b (Ab) peptides and intracellular neurofibrillary tangles composed of hyperphosphorylated tau proteins. In addition, regional loss of neurons and synapses, progressive cognitive decline and regional hypometabolism occurs (Mosconi 2005; SerranoPozo et al. 2011). Emerging evidence also suggest that, intraneuronal Ab oligomers may contribute substantially to AD disease progression (Haass and Selkoe 2007).There is no definite biomarker for the diagnosis of AD, which motivates the search for neuroimaging markers that may facilitate early detection of the disease. Using 1 H magnetic resonance spectroscopy (MRS), the regional concentration of low-molecular-weight metabolites can be measured non-invasively and provides insight into neurochemical processes of normal and pathological conditions in vivo. Performing 1 H MRS of patients with AD has revealed a consistent pattern of decreased levels of Nacetylaspartate (NAA) or NAA/total creatine (tCr) and increased myo-inositol (mIns) or mIns/tCr (Kantarci et al. 2003;Shiino et al. 2012). NAA is synthesised in neurons (Wiame et al. 2010) Abbreviations used: AD, Alzheimer's disease; APP, amyloid precursor protein; Ab, amyloid beta; CMR glc , cerebral metabolic rate of glucose; CRLB, Cramer-Rao lower bounds; DH, dorsal hippocampus; FCX, frontal cortex; GS, glutamine synthetase; mIns, myo-inositol; MRI, magnetic resonance imaging; MRS, magnetic resona...

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Section: Myo-inositol Glutamine and Taurinementioning

confidence: 95%

Altered neurochemical profile in the McGill‐R‐Thy1‐APP rat model of Alzheimer's disease: a longitudinal in vivo¹H MRS study

Nilsen

Melø

Sæther

et al. 2012

Journal of Neurochemistry

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“…Taurine was shown to inhibit L-, N-, and P/Q-voltage-gated calcium channels (Wu et al 2005 ;Liu et al 2006 ). Another mechanism by which taurine opposes the actions of glutamate, albeit indirect, involves the opening of Cl − channels by taurine demonstrated in various neuronal preparations (Yarbrough et al 1981 ;Oja et al 1990 ;Belluzzi et al 2004 ).…”

Section: +mentioning

confidence: 97%

Taurine Targets the GluN2b-Containing NMDA Receptor Subtype

et al. 2015

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“…The reaction was carried out in 25 μl using SYBR ® GREEN PCR Master Mix (Applied Biosystems) according to the manufacturers' instructions. PCR was monitored using the ABI PRISM 7000 Sequence Detection System (Applied Biosystems).Preparation of primary neuronal culture-Whole-brain primary neuronal cultures were prepared from fetal rat brains obtained from female Sprague-Dawley rats as previously described (16,17). Briefly, brains dissected from fetal rats were mechanically dissociated in basal medium Eagle (BME) supplemented with 7.6 mM sodium bicar-bonate, 26.8 mM glucose, 2 mM glutamine, and 20% heat-inactivated fetal bovine serum.…”

mentioning

confidence: 99%

Role of μ-calpain in proteolytic cleavage of brain l-glutamic acid decarboxylase

Sha

Jin

et al. 2008

Brain Research

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Glutamic acid decarboxylase (GAD) is the rate-limiting enzyme for γ-aminobutyric acid (GABA) biosynthesis. Previously, we reported the presence of truncated forms of GAD in vivo and in vitro. In addition, an unidentified endogenous protease responsible for proteolytic cleavage of full-length GAD (fGAD) to its truncated form (tGAD) was also observed. In this communication, we report that μ-calpain is a good candidate for conversion of fGAD 67 to tGAD 67 . This conclusion is based on the following observations: 1. Purified recombinant GAD 67 is cleaved by μ-calpain at specific sites; 2. In brain synaptosomal preparation, GAD 67 is cleaved to its truncated form by an endogenous protease which is inhibited by specific calpain inhibitors; 3. In μ-calpain knockout mice, the level of tGAD in the brain is greatly reduced compared with the wild type; 4. when μ-calpain gene is silenced by siRNA, the level of tGAD is also markedly reduced compared to the control group; 5. μ-calpain is activated by neuronal stimulation and Ca 2+ -influx. The physiological significance of calpain in regulation of GABA synthesis and GABAergic neurotransmission is also discussed. KeywordsCalpain; GABA synthesis; GAD; Proteolytic CleavageIn the central nervous system (CNS), γ-aminobutyric acid (GABA) is synthesized by a single enzymatic reaction catalyzed by L-glutamic decarboxylase (EC 4.1.1.15; GAD) (1,2). Mammalian species express two isoforms of GAD, namely, GAD 65 and GAD 67 , referring to GAD with a molecular weight of 65 kDa and 67 kDa, respectively. Previously, we reported **Address correspondence and reprint requests to Dr. Jang-Yen Wu, Florida Atlantic University, Department of Biomedical Science, 777 Glades Road, Boca Raton, FL 33431-0991, U.S. ; Email: jwu@fau.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript the presence of the truncated GAD (tGAD) derived from proteolytic cleavage of the full-length (fGAD) in vivo as well as in vitro (3,4). The presence of smaller forms of GAD was also observed from other laboratories (5-8). However, no information was reported regarding the identity of the endogenous proteases responsible for GAD cleavage and their physiological significance. Recently, we found that recombinant human brain GAD 65 is specifically cleaved at arginine 69 from the N-terminal of fGAD 65 to produce tGAD 65 , which is ∼2-3 fold more active than fGAD 65 (3). In addition, GAD 67 was found to be cleaved at two specific sites, one at arginine 70 and another at arginine 90, to produ...

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Mode of action of taurine as a neuroprotector

Cited by 146 publications

References 44 publications

Altered neurochemical profile in the McGill‐R‐Thy1‐APP rat model of Alzheimer's disease: a longitudinal in vivo¹H MRS study

Altered neurochemical profile in the McGill‐R‐Thy1‐APP rat model of Alzheimer's disease: a longitudinal in vivo¹H MRS study

Taurine Targets the GluN2b-Containing NMDA Receptor Subtype

Role of μ-calpain in proteolytic cleavage of brain l-glutamic acid decarboxylase

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Mode of action of taurine as a neuroprotector

Cited by 146 publications

References 44 publications

Altered neurochemical profile in the McGill‐R‐Thy1‐APP rat model of Alzheimer's disease: a longitudinal in vivo1H MRS study

Altered neurochemical profile in the McGill‐R‐Thy1‐APP rat model of Alzheimer's disease: a longitudinal in vivo1H MRS study

Taurine Targets the GluN2b-Containing NMDA Receptor Subtype

Role of μ-calpain in proteolytic cleavage of brain l-glutamic acid decarboxylase

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Altered neurochemical profile in the McGill‐R‐Thy1‐APP rat model of Alzheimer's disease: a longitudinal in vivo¹H MRS study

Altered neurochemical profile in the McGill‐R‐Thy1‐APP rat model of Alzheimer's disease: a longitudinal in vivo¹H MRS study