Calcium signaling and molecular mechanisms underlying neurodegenerative diseases.

Calcium (Ca2+) is a ubiquitous second messenger that regulates various activities in eukaryotic cells. Especially important role calcium plays in excitable cells. Neurons require extremely precise spatial-temporal control of calcium-dependent processes because they regulate such vital functions as synaptic plasticity. Recent evidence indicates that neuronal calcium signaling is abnormal in many of neurodegenerative disorders such as Alzheimer's disease (AD), Huntington's disease (HD) and Parkinson's disease (PD). These diseases represent a major medical, social, financial and scientific problem, but despite enormous research efforts, they are still incurable and only symptomatic relief drugs are available. Thus, new approaches and targets are needed. This review highlight neuronal calcium-signaling abnormalities in these diseases, with particular emphasis on the role of neuronal store-operated Ca2+ entry (SOCE) pathway and its potential relevance as a therapeutic target for treatment of neurodegeneration.

[1]  C. Cotman,et al.  Alzheimer's Presenilin-1 Mutation Potentiates Inositol 1,4,5-Trisphosphate-Mediated Calcium Signaling in Xenopus , 1999 .

[2]  M. Brotto,et al.  Azumolene Inhibits a Component of Store-operated Calcium Entry Coupled to the Skeletal Muscle Ryanodine Receptor* , 2006, Journal of Biological Chemistry.

[3]  M. Berridge.  Neuronal Calcium Signaling , 1998, Neuron.

[4]  S. Lipton.  Paradigm shift in neuroprotection by NMDA receptor blockade: Memantine and beyond , 2006, Nature Reviews Drug Discovery.

[5]  I. Bezprozvanny,et al.  STIM2 protects hippocampal mushroom spines from amyloid synaptotoxicity , 2015, Molecular Neurodegeneration.

[6]  M. Eckenhoff,et al.  Dantrolene ameliorates cognitive decline and neuropathology in Alzheimer triple transgenic mice , 2012, Neuroscience Letters.

[7]  Brij B. Singh,et al.  TRPC1 protects human SH-SY5Y cells against salsolinol-induced cytotoxicity by inhibiting apoptosis , 2006, Brain Research.

[8]  B. de Strooper,et al.  Familial Alzheimer disease-linked mutations specifically disrupt Ca2+ leak function of presenilin 1. , 2007, The Journal of clinical investigation.

[9]  M. Farrer,et al.  Advances in the genetics of Parkinson disease , 2013, Nature Reviews Neurology.

[10]  M. Brini,et al.  Emerging (and converging) pathways in Parkinson's disease: keeping mitochondrial wellness. , 2017, Biochemical and biophysical research communications.

[11]  K. Wada,et al.  Calcium leak through ryanodine receptor is involved in neuronal death induced by mutant huntingtin. , 2012, Biochemical and biophysical research communications.

[12]  L. Raymond,et al.  Increased Sensitivity to N-Methyl-D-Aspartate Receptor-Mediated Excitotoxicity in a Mouse Model of Huntington's Disease , 2002, Neuron.

[13]  L. Raymond,et al.  Calpain and STriatal-Enriched protein tyrosine phosphatase (STEP) activation contribute to extrasynaptic NMDA receptor localization in a Huntington's disease mouse model. , 2012, Human molecular genetics.

[14]  D. Theobald.  Presenilin adopts the ClC channel fold , 2016, Protein science : a publication of the Protein Society.

[15]  Yigong Shi,et al.  Structure of a presenilin family intramembrane aspartate protease , 2012, Nature.

[16]  P. Dodd,et al.  Selective loss of NMDA receptor NR1 subunit isoforms in Alzheimer's disease , 2004, Journal of neurochemistry.

[17]  I. Bezprozvanny,et al.  Dysregulation of neuronal calcium homeostasis in Alzheimer's disease - A therapeutic opportunity? , 2017, Biochemical and biophysical research communications.

[18]  M. Zhu,et al.  A role for Orai in TRPC-mediated Ca2+ entry suggests that a TRPC:Orai complex may mediate store and receptor operated Ca2+ entry , 2009, Proceedings of the National Academy of Sciences.

[19]  John Hardy,et al.  The amyloid hypothesis for Alzheimer’s disease: a critical reappraisal , 2009, Journal of neurochemistry.

[20]  D. James Surmeier,et al.  ‘Rejuvenation’ protects neurons in mouse models of Parkinson’s disease , 2007, Nature.

[21]  D. Surmeier,et al.  Physiological phenotype and vulnerability in Parkinson's disease. , 2012, Cold Spring Harbor perspectives in medicine.

[22]  W. Klein,et al.  Aβ Oligomers Induce Neuronal Oxidative Stress through an N-Methyl-D-aspartate Receptor-dependent Mechanism That Is Blocked by the Alzheimer Drug Memantine* , 2007, Journal of Biological Chemistry.

[23]  P. Hiesinger,et al.  The synaptic maintenance problem: membrane recycling, Ca2+ homeostasis and late onset degeneration , 2013, Molecular Neurodegeneration.

[24]  Xibao Liu,et al.  Contribution of TRPC1 and Orai1 to Ca(2+) entry activated by store depletion. , 2011, Advances in experimental medicine and biology.

[25]  S. Lipton.  Pathologically activated therapeutics for neuroprotection , 2007, Nature Reviews Neuroscience.

[26]  Sufia Sadaf,et al.  Store-Operated Calcium Entry through Orai Is Required for Transcriptional Maturation of the Flight Circuit in Drosophila , 2015, The Journal of Neuroscience.

[27]  J. Putney,et al.  Store-operated calcium channels. , 2005, Physiological reviews.

[28]  L. Raymond,et al.  Altered NMDA Receptor Trafficking in a Yeast Artificial Chromosome Transgenic Mouse Model of Huntington's Disease , 2007, The Journal of Neuroscience.

[29]  I. Bezprozvanny.  Calcium signaling and neurodegenerative diseases. , 2009, Trends in molecular medicine.

[30]  F. LaFerla,et al.  Enhanced Ryanodine Receptor Recruitment Contributes to Ca2+ Disruptions in Young, Adult, and Aged Alzheimer's Disease Mice , 2006, The Journal of Neuroscience.

[31]  P. Koulen,et al.  The N-terminus of presenilin-2 increases single channel activity of brain ryanodine receptors through direct protein-protein interaction. , 2008, Cell calcium.

[32]  Onn Brandman,et al.  STIM2 Is a Feedback Regulator that Stabilizes Basal Cytosolic and Endoplasmic Reticulum Ca2+ Levels , 2007, Cell.

[33]  Michael J. Berridge,et al.  Calcium Signalling and Alzheimer’s Disease , 2011, Neurochemical Research.

[34]  Ernesto Carafoli,et al.  Neuronal calcium signaling: function and dysfunction , 2014, Cellular and Molecular Life Sciences.

[35]  D. Kang,et al.  Lack of Evidence for Presenilins as Endoplasmic Reticulum Ca2+ Leak Channels* , 2012, The Journal of Biological Chemistry.

[36]  Brian J. Bacskai,et al.  Aβ Plaques Lead to Aberrant Regulation of Calcium Homeostasis In Vivo Resulting in Structural and Functional Disruption of Neuronal Networks , 2008, Neuron.

[37]  D. Surmeier,et al.  Calcium and Parkinson's disease. , 2017, Biochemical and biophysical research communications.

[38]  H. Qing,et al.  TRPC1 protects dopaminergic SH-SY5Y cells from MPP+, salsolinol, and N-methyl-(R)-salsolinol-induced cytotoxicity. , 2014, Acta biochimica et biophysica Sinica.

[39]  L. Raymond,et al.  Early Increase in Extrasynaptic NMDA Receptor Signaling and Expression Contributes to Phenotype Onset in Huntington's Disease Mice , 2010, Neuron.

[40]  Ramón Cacabelos,et al.  Parkinson’s Disease: From Pathogenesis to Pharmacogenomics , 2017, International journal of molecular sciences.

[41]  L. Raymond.  Striatal synaptic dysfunction and altered calcium regulation in Huntington disease. , 2017, Biochemical and biophysical research communications.

[42]  Ivan V. Goussakov,et al.  NMDA-Mediated Ca2+ Influx Drives Aberrant Ryanodine Receptor Activation in Dendrites of Young Alzheimer's Disease Mice , 2010, The Journal of Neuroscience.

[43]  S. Feske,et al.  Reduced Synaptic STIM2 Expression and Impaired Store-Operated Calcium Entry Cause Destabilization of Mature Spines in Mutant Presenilin Mice , 2014, Neuron.

[44]  Aaron B Bowen,et al.  Local and Use-Dependent Effects of β-Amyloid Oligomers on NMDA Receptor Function Revealed by Optical Quantal Analysis , 2016, The Journal of Neuroscience.

[45]  V. Bolotina.  Orai, STIM1 and iPLA2β: a view from a different perspective , 2008, The Journal of physiology.

[46]  P Riederer,et al.  Alterations in expression of glutamatergic transporters and receptors in sporadic Alzheimer's disease. , 2007, Journal of Alzheimer's disease : JAD.

[47]  P. Koulen,et al.  The cytosolic N-terminus of presenilin-1 potentiates mouse ryanodine receptor single channel activity. , 2008, The international journal of biochemistry & cell biology.

[48]  B. de Strooper,et al.  Mutagenesis Mapping of the Presenilin 1 Calcium Leak Conductance Pore* , 2011, The Journal of Biological Chemistry.

[49]  K. Oka,et al.  Internal Ca2+ mobilization is altered in fibroblasts from patients with Alzheimer disease. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[50]  J. Hardy,et al.  A Critique of the Drug Discovery and Phase 3 Clinical Programs Targeting the Amyloid Hypothesis for Alzheimer Disease , 2014, Annals of neurology.

[51]  D. Danielpour,et al.  The Presenilin-2 Loop Peptide Perturbs Intracellular Ca2+ Homeostasis and Accelerates Apoptosis* , 2006, Journal of Biological Chemistry.

[52]  I. Bezprozvanny,et al.  Neuronal store-operated calcium entry pathway as a novel therapeutic target for Huntington's disease treatment. , 2011, Chemistry & biology.

[53]  C. Briggs,et al.  Emerging pathways driving early synaptic pathology in Alzheimer's disease. , 2017, Biochemical and biophysical research communications.

[54]  Joseph P. Yuan,et al.  STIM1 heteromultimerizes TRPC channels to determine their function as store-operated channels , 2007, Nature Cell Biology.

[55]  T. Foster,et al.  Frontiers in Aging Neuroscience Aging Neuroscience Review Article Nmda Receptors , 2022 .

[56]  P. Greengard,et al.  Regulation of NMDA receptor trafficking by amyloid-β , 2005, Nature Neuroscience.

[57]  Ilya Bezprozvanny,et al.  Neuronal calcium mishandling and the pathogenesis of Alzheimer's disease , 2008, Trends in Neurosciences.

[58]  C. Cepeda,et al.  Differential Synaptic and Extrasynaptic Glutamate-Receptor Alterations in Striatal Medium-Sized Spiny Neurons of Aged YAC128 Huntington’s Disease Mice , 2014, PLoS currents.

[59]  Roy W Jones,et al.  Drug development in Alzheimer’s disease: the path to 2025 , 2016, Alzheimer's Research & Therapy.

[60]  J. Kuźnicki,et al.  SOCE in neurons: Signaling or just refilling? , 2015, Biochimica et biophysica acta.

[61]  X. Chen,et al.  Neuroprotective Effects of Inositol 1,4,5-Trisphosphate Receptor C-Terminal Fragment in a Huntington's Disease Mouse Model , 2009, The Journal of Neuroscience.

[62]  I. Bezprozvanny,et al.  Enhanced Store-Operated Calcium Entry Leads to Striatal Synaptic Loss in a Huntington's Disease Mouse Model , 2016, The Journal of Neuroscience.

[63]  T. Capiod.  Extracellular Calcium Has Multiple Targets to Control Cell Proliferation. , 2016, Advances in experimental medicine and biology.

[64]  L. Raymond,et al.  Alterations in STriatal‐Enriched protein tyrosine Phosphatase expression, activation, and downstream signaling in early and late stages of the YAC128 Huntington's disease mouse model , 2014, Journal of neurochemistry.

[65]  E. Rojas,et al.  Alzheimer disease amyloid beta protein forms calcium channels in bilayer membranes: blockade by tromethamine and aluminum. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[66]  J. Hardy,et al.  The Amyloid Hypothesis of Alzheimer ’ s Disease : Progress and Problems on the Road to Therapeutics , 2009 .

[67]  F. LaFerla,et al.  SERCA pump activity is physiologically regulated by presenilin and regulates amyloid β production , 2008, The Journal of cell biology.

[68]  S. Zaichick,et al.  The role of Ca2+ signaling in Parkinson's disease , 2017, Disease Models & Mechanisms.

[69]  J. Kuźnicki,et al.  Presenilin-dependent expression of STIM proteins and dysregulation of capacitative Ca2+ entry in familial Alzheimer's disease. , 2009, Biochimica et biophysica acta.

[70]  B. de Strooper,et al.  Role of Presenilins in Neuronal Calcium Homeostasis , 2010, The Journal of Neuroscience.

[71]  D. James Surmeier,et al.  Robust Pacemaking in Substantia Nigra Dopaminergic Neurons , 2009, The Journal of Neuroscience.

[72]  S. Fleming,et al.  Mechanisms of Gene-Environment Interactions in Parkinson’s Disease , 2017, Current Environmental Health Reports.

[73]  R. Barker,et al.  Advancing pharmacotherapy for treating Huntington’s disease: a review of the existing literature , 2016, Expert opinion on pharmacotherapy.

[74]  L. Good,et al.  The role of ryanodine receptor type 3 in a mouse model of Alzheimer disease , 2014, Channels.

[75]  Shahid Hameed,et al.  Crosstalk between huntingtin and syntaxin 1A regulates N-type calcium channels , 2005, Molecular and Cellular Neuroscience.

[76]  J. Olson,et al.  Huntingtin Interacting Proteins Are Genetic Modifiers of Neurodegeneration , 2007, PLoS genetics.

[77]  B. Bean,et al.  Roles of Subthreshold Calcium Current and Sodium Current in Spontaneous Firing of Mouse Midbrain Dopamine Neurons , 2007, The Journal of Neuroscience.

[78]  T. Smani,et al.  Activation Mechanism for CRAC Current and Store-operated Ca2+ Entry , 2006, Journal of Biological Chemistry.

[79]  W. Klein,et al.  Aβ Oligomer-Induced Aberrations in Synapse Composition, Shape, and Density Provide a Molecular Basis for Loss of Connectivity in Alzheimer's Disease , 2007, The Journal of Neuroscience.

[80]  M. Mattson,et al.  Capacitative Calcium Entry Deficits and Elevated Luminal Calcium Content in Mutant Presenilin-1 Knockin Mice , 2000, The Journal of cell biology.

[81]  Michael R. Hayden,et al.  Balance between synaptic versus extrasynaptic NMDA receptor activity influences inclusions and neurotoxicity of mutant huntingtin , 2009, Nature Medicine.

[82]  L. Fugger,et al.  Use of calcium channel blockers and Parkinson's disease. , 2012, American journal of epidemiology.

[83]  J. Cummings,et al.  Alzheimer’s disease drug-development pipeline: few candidates, frequent failures , 2014, Alzheimer's Research & Therapy.

[84]  I. Ferreira,et al.  Dysfunctional synapse in Alzheimer's disease – A focus on NMDA receptors , 2014, Neuropharmacology.

[85]  Z. Khachaturian.  Introduction and Overview , 1989, Annals of the New York Academy of Sciences.

[86]  Minghua Wu,et al.  Dysfunction of NMDA receptors in Alzheimer’s disease , 2016, Neurological Sciences.

[87]  K. Jellinger.  Significance of brain lesions in Parkinson disease dementia and Lewy body dementia. , 2009, Frontiers of neurology and neuroscience.

[88]  H. Bading,et al.  Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders , 2010, Nature Reviews Neuroscience.

[89]  Philip Smith,et al.  Identification and characterization of the STIM (stromal interaction molecule) gene family: coding for a novel class of transmembrane proteins. , 2001, The Biochemical journal.

[90]  T. Iwatsubo,et al.  Gain-of-Function Enhancement of IP3 Receptor Modal Gating by Familial Alzheimer’s Disease–Linked Presenilin Mutants in Human Cells and Mouse Neurons , 2010, Science Signaling.

[91]  Samuel Bandara,et al.  Regulators of Calcium Homeostasis Identified by Inference of Kinetic Model Parameters from Live Single Cells Perturbed by siRNA , 2013, Science Signaling.

[92]  B. Strooper,et al.  The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics , 2011, Nature Reviews Drug Discovery.

[93]  S. Jick,et al.  Use of antihypertensives and the risk of Parkinson disease , 2008, Neurology.

[94]  C. Cepeda,et al.  Location, Location, Location: Contrasting Roles of Synaptic and Extrasynaptic NMDA Receptors in Huntington's Disease , 2010, Neuron.

[95]  V. Lee,et al.  Mechanism of Ca2+ Disruption in Alzheimer's Disease by Presenilin Regulation of InsP3 Receptor Channel Gating , 2008, Neuron.

[96]  B. Strooper,et al.  Presenilins Form ER Ca2+ Leak Channels, a Function Disrupted by Familial Alzheimer's Disease-Linked Mutations , 2006, Cell.

[97]  J. Richardson,et al.  Stabilizing ER Ca2+ Channel Function as an Early Preventative Strategy for Alzheimer’s Disease , 2012, PloS one.

[98]  Ilya Bezprozvanny,et al.  Calcium signaling, excitability, and synaptic plasticity defects in a mouse model of Alzheimer's disease. , 2015, Journal of Alzheimer's disease : JAD.

[99]  L. Raymond,et al.  Subtype‐Specific Enhancement of NMDA Receptor Currents by Mutant Huntingtin , 1999, Journal of neurochemistry.

[100]  J. Díaz,et al.  Aβ ion channels. Prospects for treating Alzheimer's disease with Aβ channel blockers , 2007 .

[101]  K. Kawasaki,et al.  Amyloid β Protein Potentiates Ca2+ Influx Through L‐Type Voltage‐Sensitive Ca2+ Channels: A Possible Involvement of Free Radicals , 1997, Journal of neurochemistry.

[102]  A. Grünewald,et al.  Genetics of Parkinson's Disease , 2011, Seminars in neurology.

[103]  M. Frosch,et al.  Presenilin-Mediated Modulation of Capacitative Calcium Entry , 2000, Neuron.

[104]  Grace E Stutzmann,et al.  Dysregulated IP3 Signaling in Cortical Neurons of Knock-In Mice Expressing an Alzheimer's-Linked Mutation in Presenilin1 Results in Exaggerated Ca2+ Signals and Altered Membrane Excitability , 2004, The Journal of Neuroscience.

[105]  R. Llinás,et al.  Disturbed Ca2+ signaling and apoptosis of medium spiny neurons in Huntington's disease. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[106]  Vishnu Suppiramaniam,et al.  Amyloid beta peptides and glutamatergic synaptic dysregulation , 2008, Experimental Neurology.

[107]  T. Foster,et al.  Central role for NMDA receptors in redox mediated impairment of synaptic function during aging and Alzheimer’s disease , 2017, Behavioural Brain Research.

[108]  D. Surmeier,et al.  The L-type channel antagonist isradipine is neuroprotective in a mouse model of Parkinson's disease , 2011, Neurobiology of Disease.

[109]  A. Draguhn,et al.  Amyloid β Oligomers (Aβ1–42 Globulomer) Suppress Spontaneous Synaptic Activity by Inhibition of P/Q-Type Calcium Currents , 2008, The Journal of Neuroscience.

[110]  B. Bergmans,et al.  γ-secretases: from cell biology to therapeutic strategies , 2010, The Lancet Neurology.

[111]  M. Hayden,et al.  Huntingtin and Huntingtin-Associated Protein 1 Influence Neuronal Calcium Signaling Mediated by Inositol-(1,4,5) Triphosphate Receptor Type 1 , 2003, Neuron.

[112]  D. Bennett,et al.  Altered ryanodine receptor expression in mild cognitive impairment and Alzheimer's disease , 2012, Neurobiology of Aging.

[113]  D. Armstrong,et al.  Functional interactions among Orai1, TRPCs, and STIM1 suggest a STIM-regulated heteromeric Orai/TRPC model for SOCE/Icrac channels , 2008, Proceedings of the National Academy of Sciences.

[114]  D. Bansal,et al.  Reduced Risk of Parkinson's Disease in Users of Calcium Channel Blockers: A Meta-Analysis , 2015, International journal of chronic diseases.

[115]  M. Mattson,et al.  Presenilin-1 Mutations Increase Levels of Ryanodine Receptors and Calcium Release in PC12 Cells and Cortical Neurons* , 2000, The Journal of Biological Chemistry.

[116]  Jane S. Paulsen,et al.  A new model for prediction of the age of onset and penetrance for Huntington's disease based on CAG length , 2004, Clinical genetics.

[117]  J. Molgó,et al.  Early Presynaptic and Postsynaptic Calcium Signaling Abnormalities Mask Underlying Synaptic Depression in Presymptomatic Alzheimer's Disease Mice , 2012, The Journal of Neuroscience.

[118]  King-Ho Cheung,et al.  Familial Alzheimer’s disease–associated presenilin 1 mutants promote γ-secretase cleavage of STIM1 to impair store-operated Ca2+ entry , 2016, Science Signaling.

[119]  M. Kirber,et al.  Impairment of PARK14-dependent Ca2+ signalling is a novel determinant of Parkinson's disease , 2016, Nature Communications.

[120]  Brij B. Singh,et al.  TRPC1-mediated Inhibition of 1-Methyl-4-phenylpyridinium Ion Neurotoxicity in Human SH-SY5Y Neuroblastoma Cells* , 2005, Journal of Biological Chemistry.

[121]  Marisa Brini,et al.  Calcium signaling in Parkinson’s disease , 2014, Cell and Tissue Research.

[122]  L. Raymond,et al.  Chronic blockade of extrasynaptic NMDA receptors ameliorates synaptic dysfunction and pro-death signaling in Huntington disease transgenic mice , 2014, Neurobiology of Disease.

[123]  F. LaFerla,et al.  Presenilin-2 Mutations Modulate Amplitude and Kinetics of Inositol 1,4,5-Trisphosphate-mediated Calcium Signals* , 1999, The Journal of Biological Chemistry.

[124]  M. Madesh,et al.  STIM proteins: dynamic calcium signal transducers , 2012, Nature Reviews Molecular Cell Biology.

[125]  Y. Auberson,et al.  Amyloid beta peptide 1-42 disturbs intracellular calcium homeostasis through activation of GluN2B-containing N-methyl-d-aspartate receptors in cortical cultures. , 2012, Cell Calcium.

[126]  I. Bezprozvanny,et al.  Store-Operated Calcium Channel Complex in Postsynaptic Spines: A New Therapeutic Target for Alzheimer's Disease Treatment , 2016, The Journal of Neuroscience.

[127]  M. Segal,et al.  The role of the store‐operated calcium entry channel Orai1 in cultured rat hippocampal synapse formation and plasticity , 2017, The Journal of physiology.

[128]  X. Chen,et al.  Dantrolene is neuroprotective in Huntington's disease transgenic mouse model , 2011, Molecular Neurodegeneration.

[129]  Joshua L. Plotkin,et al.  Corticostriatal synaptic adaptations in Huntington’s disease , 2015, Current Opinion in Neurobiology.

[130]  M. Prakriya,et al.  Regulation of neurogenesis by calcium signaling. , 2016, Cell calcium.

[131]  W. Ondo,et al.  A pilot study of the clinical efficacy and safety of memantine for Huntington's disease. , 2007, Parkinsonism & related disorders.

[132]  A. Dominguez-Rodriguez,et al.  Phospholipase A2 as a Molecular Determinant of Store-Operated Calcium Entry. , 2016, Advances in experimental medicine and biology.

[133]  F. Wappler,et al.  Dantrolene – A review of its pharmacology, therapeutic use and new developments , 2004, Anaesthesia.

[134]  I. Bezprozvanny,et al.  Evaluation of clinically relevant glutamate pathway inhibitors in in vitro model of Huntington's disease , 2006, Neuroscience Letters.

[135]  Z. Khachaturian,et al.  Calcium Hypothesis of Alzheimer's disease and brain aging: A framework for integrating new evidence into a comprehensive theory of pathogenesis , 2017, Alzheimer's & Dementia.

[136]  M. Martín-Satué,et al.  Amyloid β peptide oligomers directly activate NMDA receptors. , 2011, Cell calcium.

[137]  L. Birnbaumer,et al.  Inhibition of L-Type Ca2+ Channels by TRPC1-STIM1 Complex Is Essential for the Protection of Dopaminergic Neurons , 2017, The Journal of Neuroscience.

[138]  J. Parys,et al.  Intracellular Ca(2+) signaling and Ca(2+) microdomains in the control of cell survival, apoptosis and autophagy. , 2016, Cell calcium.

[139]  Manish S. Shah,et al.  A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes , 1993, Cell.

[140]  F. Benfenati,et al.  Ryanodine Receptor Blockade Reduces Amyloid-β Load and Memory Impairments in Tg2576 Mouse Model of Alzheimer Disease , 2012, The Journal of Neuroscience.

[141]  I. Bezprozvanny,et al.  Neuronal Store-Operated Calcium Entry and Mushroom Spine Loss in Amyloid Precursor Protein Knock-In Mouse Model of Alzheimer's Disease , 2015, The Journal of Neuroscience.

[142]  R. Kraft.  STIM and ORAI proteins in the nervous system , 2015, Channels.