Release Date: 2024-06-12

Degenerative Brain Diseases and Acetylcholine and Gamma–Aminobutyric Acid Metabolism

Release Date: 2024-06-12

Neurotransmitters are endogenous chemical messengers that enable communication between neurons. Neurotransmitters play a fundamental role in brain function. Changes in neurotransmitter levels can affect normal brain function. Neurotransmitter deficiency can result from damage or dysfunction of nerve cells in brain regions, which can lead to degenerative brain diseases. Altered levels of acetylcholine are associated with [...]

Media Type
    Buy from

    Price may vary by retailers

    Work TypeBook Chapter
    Published inBrain Biochemistry and Its Disease
    First Page79
    Last Page94
    DOIhttps://doi.org/10.69860/nobel.9786053359371.5
    Page Count16
    Copyright HolderNobel Tıp Kitabevleri
    Licensehttps://nobelpub.com/publish-with-us/copyright-and-licensing
    Neurotransmitters are endogenous chemical messengers that enable communication between neurons. Neurotransmitters play a fundamental role in brain function. Changes in neurotransmitter levels can affect normal brain function. Neurotransmitter deficiency can result from damage or dysfunction of nerve cells in brain regions, which can lead to degenerative brain diseases. Altered levels of acetylcholine are associated with degenerative brain diseases such as Alzheimer’s disease. Dysfunction of the GABA system is associated with different degenerative brain diseases such as epilepsy, schizophrenia and autism spectrum disorder.

    Sedat Coskunsu (Author)
    Research Assistant, Mardin Artuklu University
    https://orcid.org/0000-0002-9667-7854
    3Research assistant Sedat Coşkunsu completed his master’s degree in Nutrition and Dietetics after completing his undergraduate education in nutrition and dietetics. He is currently doing his doctorate in nutrition and dietetics. among his academic contributions, he has made articles and congresses related to the field of nutrition. Research assistant Sedat Coşkunsu completed his undergraduate education in nutrition and dietetics and completed his master’s degree in nutrition and dietetics.

    • Nimgampalle M, Chakravarthy H, Sharma S, Shree S, Bhat AR, Pradeepkiran JA, et al. Neurotransmitter systems in the etiology of major neurological disorders: Emerging insights and therapeutic implications. Ageing Research Reviews. 2023:101994.

    • Pendyam S, Mohan A, Kalivas PW, Nair SS. Role of perisynaptic parameters in neurotransmitter homeostasis—computational study of a general synapse. Synapse. 2012;66(7):608-21.

    • Pradeepkiran JA, Reddy PH. Defective mitophagy in Alzheimer’s disease. Ageing Research Reviews. 2020;64:101191.

    • Reddy PH. Misfolded proteins, mitochondrial dysfunction, and neurodegenerative diseases. Biochimica et biophysica acta. 2014;1842(8):1167.

    • Teleanu RI, Niculescu A-G, Roza E, Vladâcenco O, Grumezescu AM, Teleanu DM. Neurotransmitters—Key Factors in Neurological and Neurodegenerative Disorders of the Central Nervous System. International Journal of Molecular Sciences. 2022;23(11):5954.

    • Gorman AM. Neuronal cell death in neurodegenerative diseases: recurring themes around protein handling. Journal of cellular and molecular medicine. 2008;12(6a):2263-80.

    • M Tata A, Velluto L, D'Angelo C, Reale M. Cholinergic system dysfunction and neurodegenerative diseases: cause or effect? CNS & Neurological Disorders-Drug Targets (Formerly Current Drug Targets-CNS & Neurological Disorders). 2014;13(7):1294-303.

    • Sperk G, Furtinger S, Schwarzer C, Pirker S. GABA and its receptors in epilepsy. Recent advances in epilepsy research. 2004:92-103.

    • Jahangir M, Zhou J-S, Lang B, Wang X-P. GABAergic system dysfunction and challenges in schizophrenia research. Frontiers in cell and developmental biology. 2021;9:663854.

    • Ribeiro FM, Black SA, Prado VF, Rylett RJ, Ferguson SS, Prado MA. The “ins” and “outs” of the high‐affinity choline transporter CHT1. Journal of neurochemistry. 2006;97(1):1-12.

    • Hasselmo ME. The role of acetylcholine in learning and memory. Current opinion in neurobiology. 2006;16(6):710-5.

    • Picciotto MR, Higley MJ, Mineur YS. Acetylcholine as a neuromodulator: cholinergic signaling shapes nervous system function and behavior. Neuron. 2012;76(1):116-29.

    • Gustavsson A, Norton N, Fast T, Frölich L, Georges J, Holzapfel D, et al. Global estimates on the number of persons across the Alzheimer's disease continuum. Alzheimer's & Dementia. 2023;19(2):658-70.

    • Reddy PH, Yin X, Manczak M, Kumar S, Pradeepkiran JA, Vijayan M, et al. Mutant APP and amyloid beta-induced defective autophagy, mitophagy, mitochondrial structural and functional changes and synaptic damage in hippocampal neurons from Alzheimer’s disease. Human molecular genetics. 2018;27(14):2502-16.

    • Wilcock G, Esiri M, Bowen D, Smith C. Alzheimer's disease: correlation of cortical choline acetyltransferase activity with the severity of dementia and histological abnormalities. Journal of the neurological sciences. 1982;57(2-3):407-17.

    • Ballinger EC, Ananth M, Talmage DA, Role LW. Basal forebrain cholinergic circuits and signaling in cognition and cognitive decline. Neuron. 2016;91(6):1199-218.

    • H Ferreira-Vieira T, M Guimaraes I, R Silva F, M Ribeiro F. Alzheimer's disease: targeting the cholinergic system. Current neuropharmacology. 2016;14(1):101-15.

    • Nyakas C, Granic I, Halmy LG, Banerjee P, Luiten PG. The basal forebrain cholinergic system in aging and dementia. Rescuing cholinergic neurons from neurotoxic amyloid-β42 with memantine. Behavioural Brain Research. 2011;221(2):594-603.

    • Bekdash RA. The cholinergic system, the adrenergic system and the neuropathology of Alzheimer’s disease. International Journal of Molecular Sciences. 2021;22(3):1273.

    • Kar S, Slowikowski SP, Westaway D, Mount HT. Interactions between β-amyloid and central cholinergic neurons: implications for Alzheimer’s disease. Journal of Psychiatry and Neuroscience. 2004;29(6):427-41.

    • Jiang S, Li Y, Zhang C, Zhao Y, Bu G, Xu H, et al. M1 muscarinic acetylcholine receptor in Alzheimer’s disease. Neuroscience bulletin. 2014;30:295-307.

    • DEMİR Z, TÜRKAN F. Asetilkolinesteraz ve Bütirilkolinesteraz Enzimlerinin Alzheimer Hastalığı ile İlişkisi. Journal of the Institute of Science and Technology. 2022;12(4):2386-95.

    • Singh M, Kaur M, Kukreja H, Chugh R, Silakari O, Singh D. Acetylcholinesterase inhibitors as Alzheimer therapy: from nerve toxins to neuroprotection. European journal of medicinal chemistry. 2013;70:165-88.

    • Duranti E, Villa C. Muscle Involvement in Amyotrophic Lateral Sclerosis: Understanding the Pathogenesis and Advancing Therapeutics. Biomolecules. 2023;13(11):1582.

    • Cappello V, Francolini M. Neuromuscular junction dismantling in amyotrophic lateral sclerosis. International journal of molecular sciences. 2017;18(10):2092.

    • Taylor P, Radic Z. The cholinesterases: from genes to proteins. Annual review of pharmacology and toxicology. 1994;34(1):281-320.

    • Campanari M-L, García-Ayllón M-S, Ciura S, Sáez-Valero J, Kabashi E. Neuromuscular junction impairment in amyotrophic lateral sclerosis: reassessing the role of acetylcholinesterase. Frontiers in molecular neuroscience. 2016;9:160.

    • Park SE, Kim ND, Yoo YH. Acetylcholinesterase plays a pivotal role in apoptosome formation. Cancer research. 2004;64(8):2652-5.

    • Offermanns S, Rosenthal W. Encyclopedia of molecular pharmacology: Springer; 2021.

    • McKenna MC, Dienel GA, Sonnewald U, Waagepetersen HS, Schousboe A. Energy metabolism of the brain. Basic neurochemistry: Elsevier; 2012. p. 200-31.

    • Shimmura C, Suda S, Tsuchiya KJ, Hashimoto K, Ohno K, Matsuzaki H, et al. Alteration of plasma glutamate and glutamine levels in children with high-functioning autism. PloS one. 2011;6(10):e25340.

    • Wu C, Sun D. GABA receptors in brain development, function, and injury. Metabolic brain disease. 2015;30:367-79.

    • Fatemi SH. The molecular basis of autism: Springer; 2015.

    • Owens DF, Kriegstein AR. Is there more to GABA than synaptic inhibition? Nature Reviews Neuroscience. 2002;3(9):715-27.

    • Caruncho HJ. GABA in the nervous system: the view at 50 years, DL Martin, RW Olsen,(Eds.), Lippincott Williams and Wilkins (2000), ISBN 0-7817-2267-5 (hardback). Journal of Chemical Neuroanatomy. 2003;1(26):77.

    • Gajcy K, Lochynski S, Librowski T. A role of GABA analogues in the treatment of neurological diseases. Current Medicinal Chemistry. 2010;17(22):2338-47.

    • Stell BM, Mody I. Receptors with different affinities mediate phasic and tonic GABA (A) conductances in hippocampal neurons. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2002;22(10):RC223-RC.

    • Farrant M, Nusser Z. Variations on an inhibitory theme: phasic and tonic activation of GABAA receptors. Nature Reviews Neuroscience. 2005;6(3):215-29.

    • Carver CM, Reddy DS. Neurosteroid interactions with synaptic and extrasynaptic GABA A receptors: regulation of subunit plasticity, phasic and tonic inhibition, and neuronal network excitability. Psychopharmacology. 2013;230:151-88.

    • Allen MJ, Sabir S, Sharma S. GABA receptor. 2018.

    • Braat S, Kooy RF. The GABAA receptor as a therapeutic target for neurodevelopmental disorders. Neuron. 2015;86(5):1119-30.

    • Kim YS, Yoon B-E. Altered GABAergic signaling in brain disease at various stages of life. Experimental neurobiology. 2017;26(3):122.

    • Tao W, Higgs MH, Spain WJ, Ransom CB. Postsynaptic GABAB receptors enhance extrasynaptic GABAA receptor function in dentate gyrus granule cells. Journal of Neuroscience. 2013;33(9):3738-43.

    • Duncan NW, Wiebking C, Northoff G. Associations of regional GABA and glutamate with intrinsic and extrinsic neural activity in humans—a review of multimodal imaging studies. Neuroscience & Biobehavioral Reviews. 2014;47:36-52.

    • Zafar S, Jabeen I. Structure, function, and modulation of γ-aminobutyric acid transporter 1 (GAT1) in neurological disorders: a pharmacoinformatic prospective. Frontiers in Chemistry. 2018;6:397.

    • Salpekar JA, Mishra G. Key issues in addressing the comorbidity of attention deficit hyperactivity disorder and pediatric epilepsy. Epilepsy & Behavior. 2014;37:310-5

    • Treiman DM. GABAergic mechanisms in epilepsy. Epilepsia. 2001;42:8-12.

    • Perucca E, Bialer M, White HS. New GABA-targeting therapies for the treatment of seizures and epilepsy: I. Role of GABA as a modulator of seizure activity and recently approved medications acting on the GABA system. CNS drugs. 2023;37(9):755-79

    • Horder J, Petrinovic MM, Mendez MA, Bruns A, Takumi T, Spooren W, et al. Glutamate and GABA in autism spectrum disorder—a translational magnetic resonance spectroscopy study in man and rodent models. Translational psychiatry. 2018;8(1):106.

    • Blatt GJ, Fatemi SH. Alterations in GABAergic biomarkers in the autism brain: research findings and clinical implications. The Anatomical Record. 2011;294(10):1646-52.

    • Bernardi S, Anagnostou E, Shen J, Kolevzon A, Buxbaum JD, Hollander E, et al. In vivo 1H-magnetic resonance spectroscopy study of the attentional networks in autism. Brain research. 2011;1380:198-205.

    • Kubas B, Kułak W, Sobaniec W, Tarasow E, Łebkowska U, Walecki J. Metabolite alterations in autistic children: a 1H MR spectroscopy study. Advances in medical sciences. 2012;57(1):152-6.

    • Brown MS, Singel D, Hepburn S, Rojas DC. Increased glutamate concentration in the auditory cortex of persons with autism and first‐degree relatives: a 1H‐MRS study. Autism Research. 2013;6(1):1-10.

    • Gaetz W, Bloy L, Wang D, Port RG, Blaskey L, Levy S, et al. GABA estimation in the brains of children on the autism spectrum: measurement precision and regional cortical variation. Neuroimage. 2014;86:1-9.

    • SUMMAKOĞLU D, ERTUĞRUL B. Şizofreni ve tedavisi. Lectio Scientific. 2018;2(1):43-61.

    • Öztürk S. Şizofreni Hastalarında Yaşam Kalitesinin; Pozitif Belirtiler, Negatif Belirtiler, Depresyon ve İçgörü İle İlişkisi, Zonguldak Karaelmas Üniversitesi Tıp Fakültesi Psikiyatri Anabilim Dalı Tıpta Uzmanlık Tezi, Zonguldak. Sakıcı, Ç Var, M Hocaoğlu, Ç(2014),“Türkiye’deki Ruh ve Sinir Hastalıkları Bölge Hastane Bahçelerinin Terapi Açısından Değerlendirilmesi”, Ormancılık. 2010.

    • de Jonge JC, Vinkers CH, Hulshoff Pol HE, Marsman A. GABAergic mechanisms in schizophrenia: linking postmortem and in vivo studies. Frontiers in Psychiatry. 2017;8:118.

    • Egerton A, Modinos G, Ferrera D, McGuire P. Neuroimaging studies of GABA in schizophrenia: a systematic review with meta-analysis. Translational psychiatry. 2017;7(6):e1147-e.v

    • van Nuland AJ, den Ouden HE, Zach H, Dirkx MF, van Asten JJ, Scheenen TW, et al. GABAergic changes in the thalamocortical circuit in Parkinson's disease. Human Brain Mapping. 2020;41(4):1017-29.

    • Tritsch NX, Oh W-J, Gu C, Sabatini BL. Midbrain dopamine neurons sustain inhibitory transmission using plasma membrane uptake of GABA, not synthesis. Elife. 2014;3:e01936.

    • O'Gorman Tuura RL, Baumann CR, Baumann-Vogel H. Beyond dopamine: GABA, glutamate, and the axial symptoms of Parkinson disease. Frontiers in neurology. 2018;9:806.

    • Błaszczyk JW. Parkinson's disease and neurodegeneration: GABA-collapse hypothesis. Frontiers in neuroscience. 2016;10:269.

    • Terkelsen MH, Hvingelby VS, Pavese N. Molecular Imaging of the GABAergic System in Parkinson’s Disease and Atypical Parkinsonisms. Current Neurology and Neuroscience Reports. 2022;22(12):867-79.

    Share This Chapter!