PAS kinase is a nutrient and energy sensor in hypothalamic areas required for the normal function of AMPK and mTOR/S6K1.

Abstract:

:The complications caused by overweight, obesity and type 2 diabetes are one of the main problems that increase morbidity and mortality in developed countries. Hypothalamic metabolic sensors play an important role in the control of feeding and energy homeostasis. PAS kinase (PASK) is a nutrient sensor proposed as a regulator of glucose metabolism and cellular energy. The role of PASK might be similar to other known metabolic sensors, such as AMP-activated protein kinase (AMPK) and the mammalian target of rapamycin (mTOR). PASK-deficient mice resist diet-induced obesity. We have recently reported that AMPK and mTOR/S6K1 pathways are regulated in the ventromedial and lateral hypothalamus in response to nutritional states, being modulated by anorexigenic glucagon-like peptide-1 (GLP-1)/exendin-4 in lean and obese rats. We identified PASK in hypothalamic areas, and its expression was regulated under fasting/re-feeding conditions and modulated by exendin-4. Furthermore, PASK-deficient mice have an impaired activation response of AMPK and mTOR/S6K1 pathways. Thus, hypothalamic AMPK and S6K1 were highly activated under fasted/re-fed conditions. Additionally, in this study, we have observed that the exendin-4 regulatory effect in the activity of metabolic sensors was lost in PASK-deficient mice, and the anorexigenic properties of exendin-4 were significantly reduced, suggesting that PASK could be a mediator in the GLP-1 signalling pathway. Our data indicated that the PASK function could be critical for preserving the nutrient effect on AMPK and mTOR/S6K1 pathways and maintain the regulatory role of exendin-4 in food intake. Some of the antidiabetogenic effects of exendin-4 might be modulated through these processes.

journal_name

Mol Neurobiol

journal_title

Molecular neurobiology

authors

Hurtado-Carneiro V,Roncero I,Egger SS,Wenger RH,Blazquez E,Sanz C,Alvarez E

doi

10.1007/s12035-013-8630-4

subject

Has Abstract

pub_date

2014-10-01 00:00:00

pages

314-26

issue

2

eissn

0893-7648

issn

1559-1182

journal_volume

50

pub_type

杂志文章
  • A Systematic Review of MicroRNA Expression as Biomarker of Late-Onset Alzheimer's Disease.

    abstract::Late-onset Alzheimer's disease (LOAD) is a high-occurrence neurological disorder but the difficulty in identifying precise and early biomarkers has complicated the understanding of the disease and the development of new treatments. In this sense, important knowledge is emerging regarding novel molecular and biological...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-019-01676-9

    authors: Herrera-Espejo S,Santos-Zorrozua B,Álvarez-González P,Lopez-Lopez E,Garcia-Orad Á

    更新日期:2019-12-01 00:00:00

  • Fucoxanthin Mitigates Subarachnoid Hemorrhage-Induced Oxidative Damage via Sirtuin 1-Dependent Pathway.

    abstract::Oxidative stress is a key component of the pathological cascade in subarachnoid hemorrhage (SAH). Fucoxanthin (Fx) possesses a strong antioxidant property and has shown neuroprotective effects in acute brain injuries such as ischemic stroke and traumatic brain injury. Here, we investigated the beneficial effects of Fx...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-020-02095-x

    authors: Zhang XS,Lu Y,Tao T,Wang H,Liu GJ,Liu XZ,Liu C,Xia DY,Hang CH,Li W

    更新日期:2020-12-01 00:00:00

  • Chondroitin Sulfate Impairs Neural Stem Cell Migration Through ROCK Activation.

    abstract::Brain injuries such as trauma and stroke lead to glial scar formation by reactive astrocytes which produce and secret axonal outgrowth inhibitors. Chondroitin sulfate proteoglycans (CSPG) constitute a well-known class of extracellular matrix molecules produced at the glial scar and cause growth cone collapse. The CSPG...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-017-0565-8

    authors: Galindo LT,Mundim MTVV,Pinto AS,Chiarantin GMD,Almeida MES,Lamers ML,Horwitz AR,Santos MF,Porcionatto M

    更新日期:2018-04-01 00:00:00

  • Phospholipase C Beta 1: a Candidate Signature Gene for Proneural Subtype High-Grade Glioma.

    abstract::Phospholipase C beta 1 (PLCβ1) expresses in gliomas and cultured glial cells, but its expression is barely detectable in normal glial cells. We analyzed data from Gene Expression Omnibus (GEO-GDSxxx), The Cancer Genome Atlas (TCGA), and the Repository for Molecular Brain Neoplasia Data (REMBRANDT) to explore the poten...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-015-9518-2

    authors: Lu G,Chang JT,Liu Z,Chen Y,Li M,Zhu JJ

    更新日期:2016-11-01 00:00:00

  • Activation of Mitochondrial Complex II-Dependent Respiration Is Beneficial for α-Synucleinopathies.

    abstract::Parkinson's disease and dementia with Lewy bodies are major challenges in research and clinical medicine world-wide and contribute to the most common neurodegenerative disorders. Previously, specific mitochondrial polymorphisms have been found to enhance clearance of amyloid-β from the brain of APP-transgenic mice lea...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-015-9399-4

    authors: Fröhlich C,Zschiebsch K,Gröger V,Paarmann K,Steffen J,Thurm C,Schropp EM,Brüning T,Gellerich F,Radloff M,Schwabe R,Lachmann I,Krohn M,Ibrahim S,Pahnke J

    更新日期:2016-09-01 00:00:00

  • Short-Term Fructose Feeding Induces Inflammation and Oxidative Stress in the Hippocampus of Young and Adult Rats.

    abstract::The drastic increase in the consumption of fructose encouraged the research to focus on its effects on brain physio-pathology. Although young and adults differ largely by their metabolic and physiological profiles, most of the previous studies investigated brain disturbances induced by long-term fructose feeding in ad...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-017-0518-2

    authors: Cigliano L,Spagnuolo MS,Crescenzo R,Cancelliere R,Iannotta L,Mazzoli A,Liverini G,Iossa S

    更新日期:2018-04-01 00:00:00

  • Novel Sites of Neuroprotective Action of Dimebon (Latrepirdine).

    abstract::Dimebon (latrepirdine) is an anti-histaminergic agent which belongs to a fast-growing group of "old" medicines suggested to be of therapeutic utility for pathological conditions different from their original design ("repositioning"). Here, we overview the most recent studies on Dimebon directed to pathological process...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/s12035-015-9249-4

    authors: Ustyugov A,Shevtsova E,Bachurin S

    更新日期:2015-10-01 00:00:00

  • Cellular and Molecular Aspects of Parkinson Treatment: Future Therapeutic Perspectives.

    abstract::Parkinson's disease is a neurodegenerative disorder accompanied by depletion of dopamine and loss of dopaminergic neurons in the brain that is believed to be responsible for the motor and non-motor symptoms in this disease. The main drug prescribed for Parkinsonian patients is L-dopa, which can be converted to dopamin...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/s12035-018-1419-8

    authors: Jamebozorgi K,Taghizadeh E,Rostami D,Pormasoumi H,Barreto GE,Hayat SMG,Sahebkar A

    更新日期:2019-07-01 00:00:00

  • Nicotine Significantly Improves Chronic Stress-Induced Impairments of Cognition and Synaptic Plasticity in Mice.

    abstract::The aim of this study was to examine if nicotine was able to improve cognition deficits in a mouse model of chronic mild stress. Twenty-four male C57BL/6 mice were divided into three groups: control, stress, and stress with nicotine treatment. The animal model was established by combining chronic unpredictable mild st...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-016-0012-2

    authors: Shang X,Shang Y,Fu J,Zhang T

    更新日期:2017-08-01 00:00:00

  • Applying imaging genetics to ADHD: the promises and the challenges.

    abstract::Attention deficit/hyperactivity disorder (ADHD) is one of the most prevalent childhood psychiatric disorders. During the past decades, studies have focused on its genetic background and the abnormality of the brain structure and function. Recently, an advanced technique linking these two areas, namely, the imaging gen...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/s12035-014-8683-z

    authors: Wu Z,Yang L,Wang Y

    更新日期:2014-10-01 00:00:00

  • Systemic Inflammation and Multimodal Biomarkers in Amnestic Mild Cognitive Impairment and Alzheimer's Disease.

    abstract::There is increasing evidence suggesting that one of the most relevant pathophysiological features of Alzheimer's disease (AD) is neuroinflammation, which plays an important role in the production and regulation of AD-related proteins (amyloid beta (Aβ) and Tau) and exacerbates AD pathology. Neuroinflammation can also ...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-017-0795-9

    authors: Magalhães TNC,Weiler M,Teixeira CVL,Hayata T,Moraes AS,Boldrini VO,Dos Santos LM,de Campos BM,de Rezende TJR,Joaquim HPG,Talib LL,Forlenza OV,Cendes F,Balthazar MLF

    更新日期:2018-07-01 00:00:00

  • Multi-target, neuroprotective and neurorestorative M30 improves cognitive impairment and reduces Alzheimer's-like neuropathology and age-related alterations in mice.

    abstract::Based on a multimodal drug design strategy for age-related neurodegenerative diseases, we have synthesized a multifunctional nontoxic, brain-permeable iron-chelating compound, M30, possessing the neuroprotective N-propargyl moiety of the anti-Parkinsonian drug, monoamine oxidase-B inhibitor, rasagiline and the antioxi...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-012-8304-7

    authors: Kupershmidt L,Amit T,Bar-Am O,Weinreb O,Youdim MB

    更新日期:2012-08-01 00:00:00

  • The expanding interleukin-1 family and its receptors: do alternative IL-1 receptor/signaling pathways exist in the brain?

    abstract::Interleukin-1 (IL-1) has been implicated in neuroimmune responses and has pleiotropic actions in the brain. Compelling evidence has shown that IL-1 is a major mediator of inflammation and the progression of cell death in response to brain injury and cerebral ischemia. Its expression is strongly increased in these path...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1385/MN:27:3:239

    authors: Boutin H,Kimber I,Rothwell NJ,Pinteaux E

    更新日期:2003-06-01 00:00:00

  • Prioritizing Genes Related to Nicotine Addiction Via a Multi-source-Based Approach.

    abstract::Nicotine has a broad impact on both the central and peripheral nervous systems. Over the past decades, an increasing number of genes potentially involved in nicotine addiction have been identified by different technical approaches. However, the molecular mechanisms underlying nicotine addiction remain largely unknown....

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-014-8874-7

    authors: Liu X,Liu M,Li X,Zhang L,Fan R,Wang J

    更新日期:2015-08-01 00:00:00

  • The Pharmacological Inhibition of Fatty Acid Amide Hydrolase Prevents Excitotoxic Damage in the Rat Striatum: Possible Involvement of CB1 Receptors Regulation.

    abstract::The endocannabinoid system (ECS) actively participates in several physiological processes within the central nervous system. Among such, its involvement in the downregulation of the N-methyl-D-aspartate receptor (NMDAr) through a modulatory input at the cannabinoid receptors (CBr) has been established. After its produ...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-018-1129-2

    authors: Aguilera-Portillo G,Rangel-López E,Villeda-Hernández J,Chavarría A,Castellanos P,Elmazoglu Z,Karasu Ç,Túnez I,Pedraza G,Königsberg M,Santamaría A

    更新日期:2019-02-01 00:00:00

  • Enhancing Endogenous Nitric Oxide by Whole Body Periodic Acceleration Elicits Neuroprotective Effects in Dystrophic Neurons.

    abstract::We have previously shown that inadequate dystrophin in cortical neurons in mdx mice is associated with age-dependent dyshomeostasis of resting intracellular Ca2+ ([Ca2+]i) and Na+ ([Na+]i), elevated reactive oxygen species (ROS) production, increase in neuronal damage and cognitive deficit. In this study, we assessed ...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-018-1018-8

    authors: Lopez JR,Uryash A,Kolster J,Estève E,Zhang R,Adams JA

    更新日期:2018-11-01 00:00:00

  • Antidepressant-Like Effects of CX717, a Positive Allosteric Modulator of AMPA Receptors.

    abstract::Conventional antidepressant drugs elevate the availability of monoamine neurotransmitters. However, these pharmacological therapies have limited efficacy and a slow onset of action as main limitations. New glutamatergic drugs such as ketamine have shown promise as a rapid-acting antidepressant drugs although with adve...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-020-01954-x

    authors: Gordillo-Salas M,Pascual-Antón R,Ren J,Greer J,Adell A

    更新日期:2020-08-01 00:00:00

  • Glutamatergic postsynaptic density protein dysfunctions in synaptic plasticity and dendritic spines morphology: relevance to schizophrenia and other behavioral disorders pathophysiology, and implications for novel therapeutic approaches.

    abstract::Emerging researches point to a relevant role of postsynaptic density (PSD) proteins, such as PSD-95, Homer, Shank, and DISC-1, in the pathophysiology of schizophrenia and autism spectrum disorders. The PSD is a thickness, detectable at electronic microscopy, localized at the postsynaptic membrane of glutamatergic syna...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/s12035-013-8534-3

    authors: de Bartolomeis A,Latte G,Tomasetti C,Iasevoli F

    更新日期:2014-02-01 00:00:00

  • G206D Mutation of Presenilin-1 Reduces Pen2 Interaction, Increases Aβ42/Aβ40 Ratio and Elevates ER Ca(2+) Accumulation.

    abstract::Early-onset familial Alzheimer's disease (AD) is most commonly associated with the mutations in presenilin-1 (PS1). PS1 is the catalytic component of the γ-secretase complex, which cleaves amyloid precursor protein to produce amyloid-β (Aβ), the major cause of AD. Presenilin enhancer 2 (Pen2) is critical for activatin...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-014-8969-1

    authors: Chen WT,Hsieh YF,Huang YJ,Lin CC,Lin YT,Liu YC,Lien CC,Cheng IH

    更新日期:2015-12-01 00:00:00

  • Plasma Homocysteine Levels Predict the Risk of Acute Cerebral Infarction in Patients with Carotid Artery Lesions.

    abstract::This study examined the association between elevated plasma homocysteine (Hcy) levels and the risk of acute cerebral infarction in patients with carotid artery lesions. A total of 78 patients were divided into two groups, the high Hcy group (n = 38; Hcy levels >15 umol/L) and the low Hcy group (n = 40; Hcy levels ≤15 ...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-015-9226-y

    authors: Wu W,Guan Y,Xu K,Fu XJ,Lei XF,Lei LJ,Zhang ZQ,Cheng Y,Li YQ

    更新日期:2016-05-01 00:00:00

  • Short-Lived Human Umbilical Cord-Blood-Derived Neural Stem Cells Influence the Endogenous Secretome and Increase the Number of Endogenous Neural Progenitors in a Rat Model of Lacunar Stroke.

    abstract::Stroke is the leading cause of severe disability, and lacunar stroke is related to cognitive decline and hemiparesis. There is no effective treatment for the majority of patients with stroke. Thus, stem cell-based regenerative medicine has drawn a growing body of attention due to the capabilities for trophic factor ex...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-015-9530-6

    authors: Jablonska A,Drela K,Wojcik-Stanaszek L,Janowski M,Zalewska T,Lukomska B

    更新日期:2016-11-01 00:00:00

  • Neuronal Trans-differentiation by Transcription Factors Ascl1 and Nurr1: Induction of a Dopaminergic Neurotransmitter Phenotype in Cortical GABAergic Neurons.

    abstract::Neurons with a desired neurotransmitter phenotype can be differentiated from induced pluripotent stem cells or from somatic cells only through tedious protocols with relatively low yield. Readily available cortical neurons isolated from embryonic rat brain, which have already undergone a complete neuronal differentiat...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-019-01701-x

    authors: Raina A,Mahajani S,Bähr M,Kügler S

    更新日期:2020-01-01 00:00:00

  • The Crosstalk Between Pathological Tau Phosphorylation and Mitochondrial Dysfunction as a Key to Understanding and Treating Alzheimer's Disease.

    abstract::Alzheimer's disease (AD) is the most common progressive neurodegenerative disorder. A defining hallmark of the AD brain is the presence of intraneuronal neurofibrillary tangles (NFTs) which are made up of abnormally modified tau, with aberrant phosphorylation being the most studied posttranslational modification (PTM)...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/s12035-020-02084-0

    authors: Guha S,Johnson GVW,Nehrke K

    更新日期:2020-12-01 00:00:00

  • FABP7 Protects Astrocytes Against ROS Toxicity via Lipid Droplet Formation.

    abstract::Fatty acid-binding proteins (FABPs) bind and internalize long-chain fatty acids, controlling lipid dynamics. Recent studies have proposed the involvement of FABPs, particularly FABP7, in lipid droplet (LD) formation in glioma, but the physiological significance of LDs is poorly understood. In this study, we sought to ...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-019-1489-2

    authors: Islam A,Kagawa Y,Miyazaki H,Shil SK,Umaru BA,Yasumoto Y,Yamamoto Y,Owada Y

    更新日期:2019-08-01 00:00:00

  • Neurofibromin Regulates Seizure Attacks in the Rat Pilocarpine-Induced Model of Epilepsy.

    abstract::Studies have shown that neurofibromin (NF1) restricts GABA release at inhibitory synapses and regulates dendritic spine formation, which may play an important role in temporal lobe epilepsy (TLE). NF1 expression was detected by double-label immunofluorescence, immunohistochemistry, and western blot analysis in the bra...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-015-9503-9

    authors: Ren M,Li K,Wang D,Guo J,Li J,Yang G,Long X,Shen W,Hu R,Wang X,Zeng K

    更新日期:2016-11-01 00:00:00

  • Amyotrophic lateral sclerosis and skeletal muscle: an update.

    abstract::Amyotrophic lateral sclerosis (ALS) is the most frequent adult-onset motor neuron disease characterized by degeneration of upper and lower motor neurons (MNs), generalized weakness and muscle atrophy. The "neurocentric" view of ALS assumes that the disease primarily affects motor neurons, while muscle alterations only...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章,评审

    doi:10.1007/s12035-013-8578-4

    authors: Pansarasa O,Rossi D,Berardinelli A,Cereda C

    更新日期:2014-04-01 00:00:00

  • Chromosome 4q25 Variants and Age at Onset of Ischemic Stroke.

    abstract::Recent genome-wide association studies have identified two variants rs10033464 and rs2200733 on chromosome 4q25, significantly associated with ischemic stroke risk. We conducted this study to investigate whether these two variants were associated with age at onset and prognosis of ischemic stroke in a Chinese populati...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-016-9903-5

    authors: Sun L,Tian L,Xu J,Zhang Z,Liu X

    更新日期:2017-07-01 00:00:00

  • Hepcidin Suppresses Brain Iron Accumulation by Downregulating Iron Transport Proteins in Iron-Overloaded Rats.

    abstract::Iron accumulates progressively in the brain with age, and iron-induced oxidative stress has been considered as one of the initial causes for Alzheimer's disease (AD) and Parkinson's disease (PD). Based on the role of hepcidin in peripheral organs and its expression in the brain, we hypothesized that this peptide has a...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-014-8847-x

    authors: Du F,Qian ZM,Luo Q,Yung WH,Ke Y

    更新日期:2015-08-01 00:00:00

  • Hyperpalatable Diet and Physical Exercise Modulate the Expression of the Glial Monocarboxylate Transporters MCT1 and 4.

    abstract::Hyperpalatable diets (HP) impair brain metabolism, and regular physical exercise has an apparent opposite effect. Here, we combined a prior long-term exposure to HP diet followed by physical exercise and evaluated the impact on some neuroenergetic components and on cognitive performance. We assessed the extracellular ...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-016-0119-5

    authors: Portela LV,Brochier AW,Haas CB,de Carvalho AK,Gnoato JA,Zimmer ER,Kalinine E,Pellerin L,Muller AP

    更新日期:2017-10-01 00:00:00

  • The Epilepsy-Related Protein PCDH19 Regulates Tonic Inhibition, GABAAR Kinetics, and the Intrinsic Excitability of Hippocampal Neurons.

    abstract::PCDH19 encodes for protocadherin-19 (PCDH19), a cell-adhesion molecule of the cadherin superfamily preferentially expressed in the brain. PCDH19 mutations cause a neurodevelopmental syndrome named epileptic encephalopathy, early infantile, 9 (EIEE9) characterized by seizures associated with cognitive and behavioral de...

    journal_title:Molecular neurobiology

    pub_type: 杂志文章

    doi:10.1007/s12035-020-02099-7

    authors: Serratto GM,Pizzi E,Murru L,Mazzoleni S,Pelucchi S,Marcello E,Mazzanti M,Passafaro M,Bassani S

    更新日期:2020-12-01 00:00:00