{"product_id":"the-functions-diseaserelated-dysfunctions-and-therapeutic-targeting-of-neuronal-mitochondria-9781118709238","title":"The Functions DiseaseRelated Dysfunctions and","description":"\u003cb\u003eBook Synopsis\u003c\/b\u003e\u003cbr\u003eThis book presents advances in the field of neuronal mitochondria  functions, relation to therapeutics, and pharmacology. For scientists and researchers in both industry and academia, this book provides detailed discussion, examples, and approaches, to illustrate the potential of mitochondria as therapeutic targets for neuronal diseases.\u003cbr\u003e\u003cbr\u003e Helps readers understand the regulation of mitochondrial cellular processes, such as substrate metabolism, energy production, and programmed versus sporadic cell death\u003cbr\u003e Offers insights on the development of strategies for targeted therapeutic approaches and potential personalized treatments\u003cbr\u003e Includes examples of mitochondrial drugs, development, and mitochondria-targeted approaches for more efficient treatment methods and further developments in the field\u003cbr\u003e Covers the model systems and approaches needed for the development of new drugs for the central nervous system to provide potential modern therapeutics for neurodegenerativ\u003cbr\u003e\u003cbr\u003e\u003cb\u003eTable of Contents\u003c\/b\u003e\u003cbr\u003e\u003cp\u003eContributors xiv\u003c\/p\u003e \u003cp\u003ePreface xviii\u003c\/p\u003e \u003cp\u003e\u003cb\u003eSection I Mitochondrial Structure and Ion Channels 1\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003e1 Mitochondrial Permeability Transition: A Look From a Different Angle 3\u003c\/b\u003e\u003cbr\u003e\u003ci\u003eNickolay Brustovetsky\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e1.1 Regulation of Intracellular Calcium in Neurons 3\u003c\/p\u003e \u003cp\u003e1.2 Calcium Overload and Mitochondrial Permeability Transition 4\u003c\/p\u003e \u003cp\u003e1.3 The Mitochondrial Transition Pore 8\u003c\/p\u003e \u003cp\u003e1.3.1 Evidence for ANT and VDAC as Components of the PTP 8\u003c\/p\u003e \u003cp\u003e1.3.2 Alternative Hypotheses of mPTP Composition 17\u003c\/p\u003e \u003cp\u003eAcknowledgments 22\u003c\/p\u003e \u003cp\u003eReferences 22\u003c\/p\u003e \u003cp\u003e\u003cb\u003e2 The Mitochondrial Permeability Transition Pore, the c\u003c\/b\u003e\u003cb\u003e]\u003c\/b\u003e\u003cb\u003eSubunit of the F1FO AT P Synthase, Cellular Development, and Synaptic Efficiency 31\u003c\/b\u003e\u003cbr\u003e\u003ci\u003eElizabeth A. Jonas, George A. Porter, Jr., Gisela Beutner, Nelli Mnatsakanyan and Kambiz N. Alavian\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e2.1 Introduction 32\u003c\/p\u003e \u003cp\u003e2.2 Mitochondria at the Center of Cell Metabolism and Cell Death 32\u003c\/p\u003e \u003cp\u003e2.3 Mitochondrial Inner Membrane Leak: Regulator of Metabolic Rate and Uncoupling 32\u003c\/p\u003e \u003cp\u003e2.4 Mitochondrial Inner Membrane Channels and Exchangers are Necessary for Ca2+ Cycling and Cellular Ca2+ Dynamics 33\u003c\/p\u003e \u003cp\u003e2.5 Mitochondrial Inner and Outer Membrane Channel Activity Regulates Ca2+ Re]Release from Mitochondria after Buffering 34\u003c\/p\u003e \u003cp\u003e2.6 Bcl]2 Family Proteins Regulate Pathological Outer Mitochondrial Membrane Permeabilization (MOMP) 35\u003c\/p\u003e \u003cp\u003e2.7 Pathological Inner Membrane Depolarization: Mitochondrial Permeability Transition 36\u003c\/p\u003e \u003cp\u003e2.8 The Quest for an Inner Membrane Ca2+]Sensitive Uncoupling Channel: The PT Pore 37\u003c\/p\u003e \u003cp\u003e2.8.1 Electrophysiologic Properties of the mPTP 37\u003c\/p\u003e \u003cp\u003e2.8.2 Characterization of a Molecular Complex Regulating the Pore 39\u003c\/p\u003e \u003cp\u003e2.8.3 Bcl]xL Regulates Metabolic Efficiency by Binding to the β]Subunit of the ATP Synthase 39\u003c\/p\u003e \u003cp\u003e2.8.4 CypD Binds to ATP Synthase and Regulates Permeability Transition 40\u003c\/p\u003e \u003cp\u003e2.8.5 PT Activity Regulates Cardiac Development 41\u003c\/p\u003e \u003cp\u003e2.8.6 Regulatory Molecules Do Not Form the Pore of mPTP 42\u003c\/p\u003e \u003cp\u003e2.9 The mPTP: A Molecular Definition 43\u003c\/p\u003e \u003cp\u003e2.9.1 The c]Subunit of F1FO ATP Synthase Comprises the PT Pore 43\u003c\/p\u003e \u003cp\u003e2.9.2 The c]Subunit of ATP Synthase Creates the High Conductance mPTP Pore 45\u003c\/p\u003e \u003cp\u003e2.9.3 F1 Regulates Biophysical Characteristics of the Purified c]Subunit 45\u003c\/p\u003e \u003cp\u003e2.9.4 Structural Location of the Pore within the c]Subunit Ring 48\u003c\/p\u003e \u003cp\u003e2.10 Closing of the mPTP May Enhance Mitochondrial Metabolic Plasticity and Regulate Synaptic Properties in\u003c\/p\u003e \u003cp\u003eHippocampal Neurons 49\u003c\/p\u003e \u003cp\u003e2.11 mPTP Opening Correlates with Cell Death in Acute Ischemia, ROS Damage, or Glutamate Excitotoxicity 49\u003c\/p\u003e \u003cp\u003e2.12 Pro]Apoptotic Proteolytic Cleavage Fragment of Bcl]xL Causes Large Conductance Mitochondrial Ion Channel Activity Correlated with Hypoxic Synaptic Failure: Outer Mitochondrial Channel Membrane Activity Alone or mPTP? 51\u003c\/p\u003e \u003cp\u003e2.13 S ynaptic Responses Decline during Long]Term Depression in Association with Bcl]2 Family]Regulated Mitochondrial Channel Activity 52\u003c\/p\u003e \u003cp\u003e2.14 S ynapse Loss During Neurodegenerative Disease May Require Mitochondrial Channel Activity 53\u003c\/p\u003e \u003cp\u003e2.15 Conclusions 54\u003c\/p\u003e \u003cp\u003eAcknowledgments 55\u003c\/p\u003e \u003cp\u003eReferences 55\u003c\/p\u003e \u003cp\u003e\u003cb\u003e3 Mitochondrial Channels in Neurodegeneration 65\u003cbr\u003e\u003c\/b\u003e\u003ci\u003ePablo M. Peixoto, Kathleen W. Kinnally and Evgeny Pavlov\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e3.1 Introduction 65\u003c\/p\u003e \u003cp\u003e3.2 Mitochondrial Channels in the Healthy Neuron 66\u003c\/p\u003e \u003cp\u003e3.2.1 Voltage Dependent Anion]Selective Channel is the Food Channel 66\u003c\/p\u003e \u003cp\u003e3.2.2 Protein Import Channels 67\u003c\/p\u003e \u003cp\u003e3.2.3 Mitochondrial Ca2+ Channels 74\u003c\/p\u003e \u003cp\u003e3.2.4 Mrs2 – Mg2+ Channel 75\u003c\/p\u003e \u003cp\u003e3.2.5 Mitochondrial K+ Channels 76\u003c\/p\u003e \u003cp\u003e3.2.6 Mitochondrial Centum Pico]Siemens 76\u003c\/p\u003e \u003cp\u003e3.2.7 Alkaline]Induced Anion]Selective Activity and Alkaline]Induced Anion]Selective Activity 77\u003c\/p\u003e \u003cp\u003e3.2.8 Chloride Intracellular Channels 78\u003c\/p\u003e \u003cp\u003e3.2.9 Alternative Ion Transport Pathways 78\u003c\/p\u003e \u003cp\u003e3.3 Mitochondrial Channels in the Dying Cell 79\u003c\/p\u003e \u003cp\u003e3.3.1 Apoptosis 79\u003c\/p\u003e \u003cp\u003e3.3.2 Necrosis 80\u003c\/p\u003e \u003cp\u003e3.4 Mitochondrial Channels in Neurodegenerative Diseases 83\u003c\/p\u003e \u003cp\u003e3.5 Conclusions 87\u003c\/p\u003e \u003cp\u003eReferences 87\u003c\/p\u003e \u003cp\u003e\u003cb\u003eSection II Control of Mitochondrial Signaling Networks 101\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003e4 Mitochondrial Ca2+ Transport in the Control of Neuronal Functions: Molecular and Cellular Mechanisms 103\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eYuriy M. Usachev\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e4.1 Introduction 103\u003c\/p\u003e \u003cp\u003e4.2 Physiological and Pharmacological Characteristics of Mitochondrial Ca2+ Transport in Neurons 106\u003c\/p\u003e \u003cp\u003e4.3 Molecular Components of Mitochondrial Ca2+ Transport in Neurons 110\u003c\/p\u003e \u003cp\u003e4.4 Mitochondrial Ca2+ Signaling and Neuronal Excitability 114\u003c\/p\u003e \u003cp\u003e4.5 Mitochondrial Ca2+ Cycling in the Regulation of Synaptic Transmission 115\u003c\/p\u003e \u003cp\u003e4.6 Mitochondrial Ca2+ Transport and the Regulation of Gene Expression in Neurons 118\u003c\/p\u003e \u003cp\u003e4.7 Future Directions 119\u003c\/p\u003e \u003cp\u003eAcknowledgments 120\u003c\/p\u003e \u003cp\u003eReferences 120\u003c\/p\u003e \u003cp\u003e\u003cb\u003e5 A MP\u003c\/b\u003e\u003cb\u003e]\u003c\/b\u003e\u003cb\u003eActivated Protein Kinase (AMPK) as a Cellular Energy Sensor and Therapeutic Target for Neuroprotection 130\u003cbr\u003e\u003c\/b\u003e\u003ci\u003ePetronela Weisová, Shona Pfeiffer and Jochen H. M. Prehn\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e5.1 Introduction 130\u003c\/p\u003e \u003cp\u003e5.1.1 AMPK Expression, Structure, and Activity Regulation in Brain 131\u003c\/p\u003e \u003cp\u003e5.1.2 Other Roles for AMPK 135\u003c\/p\u003e \u003cp\u003e5.1.3 AMPK in Neurological Diseases and Neurodegeneration 137\u003c\/p\u003e \u003cp\u003e5.2 Conclusion and Future Perspectives 139\u003c\/p\u003e \u003cp\u003eReferences 139\u003c\/p\u003e \u003cp\u003e\u003cb\u003e6 HDA C6: A Molecule with Multiple Functions in Neurodegenerative Diseases 146\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eYan Yan and Renjie Jiao\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e6.1 Introduction 146\u003c\/p\u003e \u003cp\u003e6.2 Molecular Properties of HDAC6 147\u003c\/p\u003e \u003cp\u003e6.2.1 Classes of the HDAC Family 147\u003c\/p\u003e \u003cp\u003e6.2.2 HDAC6 149\u003c\/p\u003e \u003cp\u003e6.3 HDAC6 and Neurodegenerative Diseases 151\u003c\/p\u003e \u003cp\u003e6.3.1 HDAC6 and Elimination of Proteotoxicity in Neurodegenerative Diseases 152\u003c\/p\u003e \u003cp\u003e6.3.2 HDAC6 and Autophagic Clearance of Dysfunctional Mitochondria 156\u003c\/p\u003e \u003cp\u003e6.4 Perspectives 158\u003c\/p\u003e \u003cp\u003eReferences 159\u003c\/p\u003e \u003cp\u003e\u003cb\u003e7 Neuronal Mitochondrial Transport 166\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eAdam L. Knight, Yanmin Chen, Tao Sun and Zu\u003c\/i\u003e\u003ci\u003e]\u003c\/i\u003e\u003ci\u003eHang Sheng\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e7.1 Introduction 166\u003c\/p\u003e \u003cp\u003e7.2 Complex Motility Patterns of Axonal Mitochondria 168\u003c\/p\u003e \u003cp\u003e7.3 Mechanisms of Mitochondrial Transport 169\u003c\/p\u003e \u003cp\u003e7.3.1 Kinesin Motors and Anterograde Transport 169\u003c\/p\u003e \u003cp\u003e7.3.2 Dynein Motors and Retrograde Transport 171\u003c\/p\u003e \u003cp\u003e7.3.3 Interplay of Opposing Motor Proteins 172\u003c\/p\u003e \u003cp\u003e7.4 Mechanisms of Axonal Mitochondrial Anchoring 172\u003c\/p\u003e \u003cp\u003e7.5 Regulation of Mitochondrial Transport by Synaptic Activity 173\u003c\/p\u003e \u003cp\u003e7.6 Mitochondrial Transport and Synaptic Transmission 174\u003c\/p\u003e \u003cp\u003e7.7 Mitochondrial Transport and Presynaptic Variability 175\u003c\/p\u003e \u003cp\u003e7.8 Mitochondrial Transport and Axonal Branching 176\u003c\/p\u003e \u003cp\u003e7.9 Mitochondrial Transport and Mitophagy 178\u003c\/p\u003e \u003cp\u003e7.10 Conclusions and New Challenges 180\u003c\/p\u003e \u003cp\u003eAcknowledgments 180\u003c\/p\u003e \u003cp\u003eReferences 181\u003c\/p\u003e \u003cp\u003e\u003cb\u003e8 Mitochondria in Control of Hypothalamic Metabolic Circuits 186\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eCarole M. Nasrallah and Tamas L. Horvath\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e8.1 Introduction 186\u003c\/p\u003e \u003cp\u003e8.2 Yin]Yang Relationship between Components of Hypothalamic Feeding and Satiety Circuits 187\u003c\/p\u003e \u003cp\u003e8.3 Mitochondria and Their Dynamics 189\u003c\/p\u003e \u003cp\u003e8.4 Metabolic Principles of Hunger and Satiety Promotion: Mitochondria in Support of Fat Versus Glucose Utilization 191\u003c\/p\u003e \u003cp\u003e8.5 Mitochondria Dynamics and Cellular Energetics 193\u003c\/p\u003e \u003cp\u003e8.5.1 Fission and Fusion of Mitochondria in Hypothalamic Feeding Circuits 194\u003c\/p\u003e \u003cp\u003e8.6 Mitochondrial Dysfunction and Metabolic Disorders 196\u003c\/p\u003e \u003cp\u003e8.7 Conclusions 197\u003c\/p\u003e \u003cp\u003eReferences 197\u003c\/p\u003e \u003cp\u003e\u003cb\u003e9 Mitochondria Anchored at the Synapse 203\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eGeorge A. Spirou, Dakota Jackson and Guy A. Perkins\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e9.1 Introduction 203\u003c\/p\u003e \u003cp\u003e9.2 Calibrated Positioning of Mitochondria 204\u003c\/p\u003e \u003cp\u003e9.3 Mitochondria and Crista Structure 206\u003c\/p\u003e \u003cp\u003e9.4 Adhering Junctions and Linkages to the Cytoskeleton 208\u003c\/p\u003e \u003cp\u003e9.5 Linkages of the OMM to the Mitochondrial Plaque and Reticulated Membrane 210\u003c\/p\u003e \u003cp\u003e9.6 Functions of the Organelle Complex 211\u003c\/p\u003e \u003cp\u003e9.7 MACs and Filamentous Contacts: A Continuum of Structure? 213\u003c\/p\u003e \u003cp\u003eAcknowledgments 214\u003c\/p\u003e \u003cp\u003eReferences 214\u003c\/p\u003e \u003cp\u003e\u003cb\u003eSection III Defective Mitochondrial Dynamics and Mitophagy 219\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003e10 Neuronal Mitochondria are Different: Relevance to Neurodegenerative Disease 221\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eSarah B. Berman and J. Marie Hardwick\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e10.1 Introduction 221\u003c\/p\u003e \u003cp\u003e10.2 Mitochondrial Dynamics in Neurons and Neurodegenerative Disease 222\u003c\/p\u003e \u003cp\u003e10.2.1 Quantifying Mitochondrial Dynamics 222\u003c\/p\u003e \u003cp\u003e10.2.2 Mutations and Toxins Alter Mitochondrial Dynamics in Neurological Disease 223\u003c\/p\u003e \u003cp\u003e10.3 Triggering Mitophagy in Neurons versus Other Cell Types 226\u003c\/p\u003e \u003cp\u003e10.3.1 Parkin Mitophagy Pathway Disease Genes 226\u003c\/p\u003e \u003cp\u003e10.3.2 Metabolic States of Neurons Modulate Mitophagy Induction 227\u003c\/p\u003e \u003cp\u003e10.3.3 Neurons Distinguish between Different Types of Mitochondrial Damage 228\u003c\/p\u003e \u003cp\u003e10.4 BCL]xL: The Guardian of Mitochondria 231\u003c\/p\u003e \u003cp\u003e10.4.1 BCL]xL Regulates Mitochondrial Dynamics and Neuronal Activity 231\u003c\/p\u003e \u003cp\u003e10.4.2 BCL]xL Regulates Mitochondrial Energetics 232\u003c\/p\u003e \u003cp\u003eAcknowledgments 233\u003c\/p\u003e \u003cp\u003eReferences 233\u003c\/p\u003e \u003cp\u003e\u003cb\u003e11 PINK1 as a Sensor for Mitochondrial Function: Dual Roles 240\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eErin Steer, Michelle Dail and Charleen T. Chu\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e11.1 Introduction 240\u003c\/p\u003e \u003cp\u003e11.2 PINK1 Promotes Mitochondrial Function 241\u003c\/p\u003e \u003cp\u003e11.3 Healthy Mitochondria Import and Process PINK1 244\u003c\/p\u003e \u003cp\u003e11.3.1 Localization and Processing of PINK1 Depends on an Intact ΔΨm 244\u003c\/p\u003e \u003cp\u003e11.4 Accumulation of Full Length]PINK1 as a Sensor of Mitochondrial Dysfunction 245\u003c\/p\u003e \u003cp\u003e11.5 Cytosolic PINK1 as a Sensor for Mitochondrial Function 247\u003c\/p\u003e \u003cp\u003e11.5.1 Cytosolic PINK1 Suppresses Cell Death and Autophagy\/Mitophagy 247\u003c\/p\u003e \u003cp\u003e11.5.2 Cytosolic PINK1 Promotes Neurite Extension and Cell Survival 248\u003c\/p\u003e \u003cp\u003e11.6 PINK1 and Mitochondrial Dynamics 248\u003c\/p\u003e \u003cp\u003e11.7 Dual Roles for PINK1 as a Sensor of Mitochondrial Function and Dysfunction 249\u003c\/p\u003e \u003cp\u003eReferences 249\u003c\/p\u003e \u003cp\u003e\u003cb\u003e12 A Get\u003c\/b\u003e\u003cb\u003e]\u003c\/b\u003e\u003cb\u003eTogether to Tear It Apart: The Mitochondrion Meets the Cellular Turnover Machinery 254\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eGian\u003c\/i\u003e\u003ci\u003e]\u003c\/i\u003e\u003ci\u003eLuca McLelland and Edward A. Fon\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e12.1 Mitochondrial Quality Control in Neurodegeneration 254\u003c\/p\u003e \u003cp\u003e12.2 An Overview of the Ubiquitin]Proteasome System 255\u003c\/p\u003e \u003cp\u003e12.3 Activities of the Cytosolic Proteasome at the Outer Mitochondrial Membrane 256\u003c\/p\u003e \u003cp\u003e12.4 The Turnover of Whole Mitochondria by Mitophagy 260\u003c\/p\u003e \u003cp\u003e12.5 Proteasomes and Phagophores Converge in the PINK1\/parkin Pathway 261\u003c\/p\u003e \u003cp\u003e12.6 Implications of PINK1]\/Parkin]Dependent Mitophagy in the Brain and in PD 265\u003c\/p\u003e \u003cp\u003e12.7 Emerging Mitochondrial Quality Control Mechanisms 267\u003c\/p\u003e \u003cp\u003eReferences 268\u003c\/p\u003e \u003cp\u003e\u003cb\u003e13 Mitochondrial Involvement in Neurodegenerative Dementia 280\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eLaura Bonanni, Valerio Frazzini, Astrid Thomas and Marco Onofrj\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e13.1 Introduction 280\u003c\/p\u003e \u003cp\u003e13.2 Mitochondrial Dysfunction in Alzheimer Disease 281\u003c\/p\u003e \u003cp\u003e13.3 Mitochondrial Dysfunction, Bioenergetic Deficits, and Oxidative Stress in AD 282\u003c\/p\u003e \u003cp\u003e13.4 Mitochondrial Fragmentation in AD 283\u003c\/p\u003e \u003cp\u003e13.5 S ynaptic Mitochondria in AD 283\u003c\/p\u003e \u003cp\u003e13.6 Mitochondrial Dysfunction and Cationic Dyshomeostasis in AD 284\u003c\/p\u003e \u003cp\u003e13.7 Mitochondrial Dysfunction in DLB 286\u003c\/p\u003e \u003cp\u003e13.8 LRRK2 Mutations, Mitochondria and DLB 287\u003c\/p\u003e \u003cp\u003e13.9 Akinetic Crisis in Synucleinopathies is Linked to Genetic Mutations Involving Mitochondrial Proteins 287\u003c\/p\u003e \u003cp\u003e13.10 Conclusions 289\u003c\/p\u003e \u003cp\u003eReferences 289\u003c\/p\u003e \u003cp\u003e\u003cb\u003eSection IV Mitochondria-Targeted Therapeutics and Model Systems 295\u003c\/b\u003e\u003c\/p\u003e \u003cp\u003e\u003cb\u003e14 Neuronal Mitochondria as a Target for the Discovery and Development of New Therapeutics 297\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eValentin K. Gribkoff\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e14.1 Neurodegenerative Disorders and the Status of Drug Discovery 297\u003c\/p\u003e \u003cp\u003e14.2 Mitochondria as Targets for the Development of New NDD Therapies 300\u003c\/p\u003e \u003cp\u003e14.3 The Effects of Dexpramipexole on Mitochondrial Conductances: An Example of an Approach for ALS and Other NDDs 301\u003c\/p\u003e \u003cp\u003e14.3.1 ALS as a Therapeutic Target 301\u003c\/p\u003e \u003cp\u003e14.3.2 Mitochondrial Dysfunction in ALS 303\u003c\/p\u003e \u003cp\u003e14.3.3 Dexpramipexole and Bioenergetic Efficiency: Preclinical Studies 303\u003c\/p\u003e \u003cp\u003e14.3.4 Dexpramipexole in the Clinic 309\u003c\/p\u003e \u003cp\u003e14.4 What is the Future of a Mitochondrial Approach for NDD Therapy? 313\u003c\/p\u003e \u003cp\u003eAcknowledgments 314\u003c\/p\u003e \u003cp\u003eReferences 315\u003c\/p\u003e \u003cp\u003e\u003cb\u003e15 Mitochondria as a Therapeutic Target for Alzheimer’s Disease 322\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eClara Hiu\u003c\/i\u003e\u003ci\u003e]\u003c\/i\u003e\u003ci\u003eLing Hung, Sally Shuk\u003c\/i\u003e\u003ci\u003e]\u003c\/i\u003e\u003ci\u003eYee Cheng, Simon Ming\u003c\/i\u003e\u003ci\u003e]\u003c\/i\u003e\u003ci\u003eYuen Lee and Raymond Chuen\u003c\/i\u003e\u003ci\u003e]\u003c\/i\u003e\u003ci\u003eChung Chang\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e15.1 Introduction 322\u003c\/p\u003e \u003cp\u003e15.2 Mitochondrial Abnormalities and Dysfunction in Alzheimer’s Disease 323\u003c\/p\u003e \u003cp\u003e15.2.1 Mitochondrial Morphology and Ultrastructure 323\u003c\/p\u003e \u003cp\u003e15.2.2 Beta Amyloid, Tau, and Mitochondria 323\u003c\/p\u003e \u003cp\u003e15.2.3 Defective Mitochondria at Synapses 325\u003c\/p\u003e \u003cp\u003e15.2.4 Impaired Mitochondrial Dynamics 325\u003c\/p\u003e \u003cp\u003e15.2.5 Oxidative Stress 326\u003c\/p\u003e \u003cp\u003e15.2.6 Ca2+ Dysregulation in Mitochondria 326\u003c\/p\u003e \u003cp\u003e15.2.7 Mitochondrial Permeability Transition Pore 327\u003c\/p\u003e \u003cp\u003e15.3 Mitochondria as a Drug Target 327\u003c\/p\u003e \u003cp\u003e15.3.1 Targeting Drugs to Mitochondria 327\u003c\/p\u003e \u003cp\u003e15.3.2 Mitochondria]Targeted Antioxidants 329\u003c\/p\u003e \u003cp\u003e15.3.3 Mitochondrial Ca2+ Pathways 330\u003c\/p\u003e \u003cp\u003e15.3.4 Mitochondrial Permeability Transition Pore 331\u003c\/p\u003e \u003cp\u003e15.3.5 Mitochondrial Dynamics 331\u003c\/p\u003e \u003cp\u003e15.3.6 Mitochondrial Metabolism 332\u003c\/p\u003e \u003cp\u003e15.3.7 Mitochondrial Biogenesis 332\u003c\/p\u003e \u003cp\u003e15.3.8 Limitations of Mitochondrial]Targeted Drugs 333\u003c\/p\u003e \u003cp\u003e15.4 Conclusions 333\u003c\/p\u003e \u003cp\u003eAcknowledgments 333\u003c\/p\u003e \u003cp\u003eReferences 334\u003c\/p\u003e \u003cp\u003e\u003cb\u003e16 Mitochondria in Parkinson’s Disease 339\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eGiuseppe Arena and Enza Maria Valente\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e16.1 Introduction 339\u003c\/p\u003e \u003cp\u003e16.2 Role of Mitochondria in Sporadic PD 340\u003c\/p\u003e \u003cp\u003e16.2.1 Complex I Deficiency and mtDNA Defects 340\u003c\/p\u003e \u003cp\u003e16.2.2 Oxidative Stress and ROS Production 341\u003c\/p\u003e \u003cp\u003e16.3 Mitochondrial Dysfunction in Monogenic PD 342\u003c\/p\u003e \u003cp\u003e16.3.1 Autosomal Dominant PD 343\u003c\/p\u003e \u003cp\u003e16.3.2 Autosomal Recessive PD 346\u003c\/p\u003e \u003cp\u003e16.4 Conclusions 350\u003c\/p\u003e \u003cp\u003eReferences 351\u003c\/p\u003e \u003cp\u003e\u003cb\u003e17 Therapeutic Targeting of Neuronal Mitochondria in Brain Injury 359\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eHeather M. Yonutas, Edward D. Hall and Patrick G. Sullivan\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e17.1 Introduction 359\u003c\/p\u003e \u003cp\u003e17.2 Mitochondria Bioenergetics 360\u003c\/p\u003e \u003cp\u003e17.3 Traumatic Brain Injury 363\u003c\/p\u003e \u003cp\u003e17.3.1 Models of TBI 364\u003c\/p\u003e \u003cp\u003e17.3.2 Secondary Injury Cascade of TBI 366\u003c\/p\u003e \u003cp\u003e17.4 Pharmaceutical Interventions 370\u003c\/p\u003e \u003cp\u003e17.4.1 Targeting Mitochondrial Dysfunction 370\u003c\/p\u003e \u003cp\u003e17.4.2 Targeting Oxidative Stress 371\u003c\/p\u003e \u003cp\u003e17.4.3 Interventions with Multiple Targets 372\u003c\/p\u003e \u003cp\u003e17.5 Conclusion 372\u003c\/p\u003e \u003cp\u003eReferences 373\u003c\/p\u003e \u003cp\u003e\u003cb\u003e18 The Use of Fibroblasts from Patients with Inherited Mitochondrial Disorders for Pathomechanistic Studies and Evaluation of Therapies 378\u003cbr\u003e\u003c\/b\u003e\u003ci\u003eDevorah Soiferman and Ann Saada\u003c\/i\u003e\u003c\/p\u003e \u003cp\u003e18.1 Introduction 378\u003c\/p\u003e \u003cp\u003e18.1.1 Identification of Mitochondrial Disorders 380\u003c\/p\u003e \u003cp\u003e18.1.2 Pathomechanism of Mitochondrial Disorders 381\u003c\/p\u003e \u003cp\u003e18.1.3 Treatment of Mitochondrial Disorders 382\u003c\/p\u003e \u003cp\u003e18.1.4 Models of Mitochondrial Disorders 383\u003c\/p\u003e \u003cp\u003e18.2 Pathomechanistic Studies of Mitochondrial Disorders in Patients’ Fibroblasts 385\u003c\/p\u003e \u003cp\u003e18.2.1 Reduced Cellular ATP 385\u003c\/p\u003e \u003cp\u003e18.2.2 Increased Oxidative Stress 386\u003c\/p\u003e \u003cp\u003e18.2.3 Reduction of Mitochondrial Membrane Potential 386\u003c\/p\u003e \u003cp\u003e18.2.4 Disruption of Calcium Homeostasis 386\u003c\/p\u003e \u003cp\u003e18.2.5 Coenzyme Q10 Deficiency 387\u003c\/p\u003e \u003cp\u003e18.2.6 Mitochondrial Dynamics and Mitophagy 387\u003c\/p\u003e \u003cp\u003e18.3 Evaluation of Therapeutic Options Using Patient Derived Fibroblasts 388\u003c\/p\u003e \u003cp\u003e18.3.1 Pharmacological Approaches 388\u003c\/p\u003e \u003cp\u003e18.3.2 Genetic Manipulation 391\u003c\/p\u003e \u003cp\u003e18.4 Conclusion 392\u003c\/p\u003e \u003cp\u003eAcknowledgments 393\u003c\/p\u003e \u003cp\u003eReferences 393\u003c\/p\u003e \u003cp\u003eIndex 399\u003c\/p\u003e","brand":"John Wiley \u0026 Sons Inc","offers":[{"title":"Default Title","offer_id":49406909120855,"sku":"9781118709238","price":152.06,"currency_code":"GBP","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0817\/1739\/5799\/files\/9781118709238.jpg?v=1730497524","url":"https:\/\/bookcurl.com\/products\/the-functions-diseaserelated-dysfunctions-and-therapeutic-targeting-of-neuronal-mitochondria-9781118709238","provider":"Book Curl","version":"1.0","type":"link"}