Cellular signaling in health and disease:
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Buch |
| Sprache: | English |
| Veröffentlicht: |
Dordrecht [u.a.]
Springer
2009
|
| Schriftenreihe: | Biological and medical physics, biomedical engineering
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| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis Klappentext |
| Beschreibung: | XVII, 470 S. zahlr. Ill., graph. Darst. |
| ISBN: | 9780387981727 |
Internformat
MARC
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| 100 | 1 | |a Beckerman, Martin |e Verfasser |4 aut | |
| 245 | 1 | 0 | |a Cellular signaling in health and disease |c Martin Beckerman |
| 264 | 1 | |a Dordrecht [u.a.] |b Springer |c 2009 | |
| 300 | |a XVII, 470 S. |b zahlr. Ill., graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 490 | 0 | |a Biological and medical physics, biomedical engineering | |
| 650 | 4 | |a Cellular signal transduction | |
| 650 | 4 | |a Metabolic Syndrome X |x metabolism | |
| 650 | 4 | |a Neoplasms |x metabolism | |
| 650 | 4 | |a Neurodegenerative Diseases |x metabolism | |
| 650 | 4 | |a Pathology, Cellular | |
| 650 | 4 | |a Signal Transduction |x physiology | |
| 650 | 0 | 7 | |a Zellkommunikation |0 (DE-588)4136131-3 |2 gnd |9 rswk-swf |
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| 856 | 4 | 2 | |m Digitalisierung UB Regensburg |q application/pdf |u http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=017684955&sequence=000004&line_number=0002&func_code=DB_RECORDS&service_type=MEDIA |3 Klappentext |
| 999 | |a oai:aleph.bib-bvb.de:BVB01-017684955 | ||
Datensatz im Suchindex
| _version_ | 1804139305429368832 |
|---|---|
| adam_text | Contents
Part I Metabolic Syndromes
1
Introduction
............................................ 3
1.1
The Cellular Signaling Machinery Makes Homeostasis
Possible
.......................................... 4
1.2
Inflammation Is Present in Diseases
.................... 4
1.3
Cholesterol Together with Inflammation Promotes
Atherosclerosis
.................................... 6
1.4
Signaling Pathways Responsible for Maintaining Cellular
Homeostasis Are Uncovered and Explored
.............. 6
1.5
Biophysical Techniques Provide Detailed Information on the
Three-Dimensional Structure of Macromolecules
......... 7
1.6
Signaling Pathways Have Been Illuminated Through Intensive
Efforts Spanning the Last
50
Years
.................... 8
1.7
Mutated, Misfolded Proteins Cause Cancer
............. 9
1.8
The
Microenvironment
Is an Important Ingredient in Cancer
Metastasis
........................................ 10
1.9
Neurons Are Cells Highly Specialized for Long-Range
Signaling
......................................... 12
1.10
Amyloids Are an Essential Ingredient in Many Diseases.
... 12
1.11
Reactive Oxygen and Nitrogen Species Carry Out
Signaling in Ways That Contribute to Health
and Disease
....................................... 15
Further Reading
......................................... 15
2
Energy Balance
......................................... 19
2.1
Hormonal Signaling by the Endocrine Pancreas
.......... 21
2.2
In Response to Signals from the Pancreas, the Liver Maintains
Glucose and
Lipid
Homeostasis
....................... 22
2.3
Energy in the Form of Lipids Is Stored and Released When
Needed in Adipose Tissue
........................... 24
2.4
Adipose Tissue Functions as an Endocrine Organ
......... 25
viii Contents
2.5
Ghrelin
Released by Endocrine Cells in the Stomach Acts in
Short-Term Feeding and
Long-Term
Energy
Management
...................................... 26
2.6
Satiation Signals Are Sent by Cells in the Gastrointestinal
Tract
............................................ 26
2.7
Brown Adipose Tissue Carries Out Adaptive (Diet-Induced
and Cold-Induced, Nonshivering) Thermogenesis
......... 27
2.8
Muscle Cells and
ß-Oxidation........................ 29
2.9
AMPK Is an Intracellular Energy Sensor and Regulator
... 31
2.10
AMPK Is Activated by Upstream Kinases and by
Depleted Energy Supply as Indicated by Increased
AMP/ATP Ratios
.................................. 33
2.11
The Hypothalamic Network Provides Feedback Signals to
Peripheral Tissues
.................................. 35
2.12
Leptin Signaling and Regulation of Energy Balance in the
Hypothalamus
.................................... 37
2.13
Ghrelin Signaling and Regulation of Energy Balance in the
Hypothalamus
.................................... 39
Further Reading
......................................... 40
3
Insulin Signaling and Type
2
Diabetes
........................ 45
3.1
Type
2
Diabetes Develops in a Series of Stages from
Overnutrition
..................................... 46
3.2
Adipose Tissue Functions as an Immune Organ
.......... 47
3.3
Metabolic Overload Occurs in Energy-Responsive
Tissues
.......................................... 48
3.4
Signal Transduction Begins with the Insulin Receptor and Its
Substrate Proteins
.................................. 50
3.5
Phosphomositide-3
-ОН
Kinase (PI3K) and the PTEN
Lipid
Phosphatase
...................................... 52
3.6
Activation of Protein Kinase
В
(PKB) and Protein Kinase
С
(PKC)
........................................... 54
3.7
GLUT4 Transport Biomechanics and Regulation
......... 56
3.8
The TOR Cassette Is the Downstream Target of
Akt
Signals
........................................... 58
3.9
Feedback Regulation of
Akt
by TORC2 and
1RS
by
TORC1/S6K
...................................... 60
3.10
Insulin Resistance Develops from Inflammation and
Metabolic Overload
................................ 60
3.11
Glucose-Stimulated Hormone Release by Pancreatic Islet
Cells
............................................ 63
3.12
Katp Channels and Their Regulation by Cellular
Fuel Status
....................................... 65
3.13
Islet
ß-Cell
Failure and Diabetic Complications
.......... 66
Further Reading
......................................... 67
Contents ix
4 Metabolie Program
Execution and Switching
.................. 71
4.1
Nuclear Receptors Are Ligand-Activated Transcription
Factors
.......................................... 71
4.2
Nuclear Receptors Contain Five or Six Domains
......... 73
4.3
The CAR Activates and Deactivates in a Manner
Distinct from Other Nuclear Receptors
................. 74
4.4
Peroxisome Proliferator-Activated Receptors Are
Lipid
Sensors and Effectors
............................... 75
4.5
Nuclear Receptors Require Coactivators and
Corepressors
...................................... 77
4.6
PGC-
1
Scaffold Protein in Regulation of
Lipid
Homeostasis
...................................... 80
4.7
FoxOs Mediate Survival, Metabolic, and Stress
Responses
........................................ 80
4.8 14-3-3
Protein Function as Small, Mobile Phosphoprotein
Binding Modules
.................................. 82
4.9
Gluconeogenesis in the Liver Is Stimulated by Glucagon
and Repressed by Insulin
............................ 83
4.10
Catecholamine Signaling Targets PGC la to Promote
Diet-Induced Thermogenesis in Brown Adipose
Tissue
........................................... 85
4.11
Caloric Restriction Extends
Lifespan
by Activating
Protective Stress Responses
.......................... 86
4.12
SIRT1 Promotes Fatty Acid Oxidation in Liver
and Skeletal Muscle
................................ 87
Further Reading
......................................... 88
5
Cholesterol
............................................. 91
5.1
Membrane Lipids Form Gels and Liquid States
.......... 91
5.2
Feedback Regulation of Cholesterol Synthesis
by Insigs
......................................... 94
5.3
Feedback Regulation of Cholesterol Synthesis
by SREBPs
....................................... 95
5.4
SREBPs, Liver X Receptors, and Farnesoid X Receptors
Regulate Transcription
.............................. 97
5.5
Lipoproteins Are Carriers of Cholesterol
and
Triglycérides
.................................. 98
5.6
Apolipoproteins are Amphipathic, Lipid-Binding
Constituents of the Lipoproteins
...................... 99
5.7
Cholesterol Comes in Two Forms
-
As
a Sterol,
i.e., as a Free Cholesterol
(FC)
Molecule, and as a Cholesterol
Ester
(CE)
........................................ 102
5.8
ABC Transporters Export Cholesterol from
Macrophages
..................................... 103
Further Reading
......................................... 104
í
Contents
6
Atherosclerosis
.......................................... 107
6.1
The Arterial Wall Consists of Three Layers
.............. 107
6.2
Cells Are Continually Subjected to Forces
............... 109
6.3
Atherosclerotic Lesions Occur Preferentially in Regions
of Disturbed Blood Flow
............................ 110
6.4
Cells Utilize Multiple Mechanotransduction Pathways
That Convey Information About Blood Flow
............ 112
6.5
Mechanotransduction Pathways Relay Information
About Blood Flow to Endothelial Caveolae and Nitric
Oxide Synthase
.................................... 112
6.6
oxLDL Is Atherogenic and Acts in Opposition to eNOS
and NO
.......................................... 113
6.7
Cell Adhesion Molecules and Chemokines Mediate
Leukocyte Migration into Sites of Inflammation
.......... 115
6.8
Leukocyte Migration Occurs Through a Multistep
Adhesion Cascade
................................. 117
6.9
Selectins Are Key Mediators of Leukocyte Tethering
and Rolling
....................................... 118
6.10
Slip and Catch Bonds Play Important Roles in
Selectin-Mediated Rolling
........................... 119
6.11
Leukocyte Arrest Through the Joint Actions
of Chemokines and Integrins
......................... 121
6.12
Epithelial Cell-to-Cell Adhesions Are Maintained
by Junctional Complexes
............................ 123
6.13
Leukocytes Enter the
Intima
by Passing In-Between
Epithelial Cells and by Passing Through Them
........... 125
6.14
Rupture of the Fibrous Cap and Not the Lesion Itself
Causes Thrombosis
................................. 126
Further Reading
......................................... 128
7
Chronic Inflammation
.................................... 131
7.1
The NF-reB Signaling Node Consists of IKKs,
I/îBs,
and NF-kBs
...................................... 132
7.2
Protein Ubiquitination Plays a Central Role in Cellular
Signaling
......................................... 135
7.3
TNFa Signaling Occurs Through Complex I
and Complex II
.................................... 137
7.4
Reactive Oxygen Species
(ROS)
Influences the Choice
Between Survival and Death
......................... 138
7.5
Toll-like Receptor
4
Responds to Bacterial
Lipopolysaccharides and Mammalian Lipids
............ 139
7.6
Downstream and into the Nucleus with NF-kBs
.......... 141
7.7
Glucocorticoids Terminate Inflammatory Responses
and Restore Homeostasis
............................
1
42
Contents xi
7.8 LXRs and PPARy in Transrepression
of Inflammation
Through SUMOylation
............................. 143
7.9
The Local
Microenvironment
Is a Key Organizational
Unit in Health and Disease
.......................... 145
7.10
The Inflammatory Response Is a Biphasic One with
Distinct Clear Up and Reconstruction Phases
............ 146
7.11
Macrophages
Are Inflammatory Cells with Key Roles
in the Body s Response to Infection and Injury
........... 147
7.12
Fibroblasts
Are Connective Tissue Cells
................ 149
7.13
Mesenchymal Stem Cells Are Located Throughout
the Body
......................................... 150
Further Reading
......................................... 150
8
Redox
Signaling
......................................... 155
8.1
Hydrogen Peroxide and Nitric Oxide Are Signaling
Molecules
........................................ 156
8.2
Nox
Enzymes
..................................... 157
8.3
Oxidation of Sulfhydryls and Hydrogen Peroxide
Signaling
......................................... 159
8.4
Nitric Oxide Synthases and Nitric Oxide Signaling
........ 162
8.5
The Frank-Starlings Law and Excitation-Contraction
Coupling
......................................... 164
8.6
Transcriptional Regulation of the Metabolic Programs
.... 166
8.7
Inappropriate S-Nitrosylation Contributes to
Neurodegenerative
Disorders
......................... 168
8.8
The Electron Transport Chain Can Generate Reactive
Oxygen Species
.................................... 170
Further Reading
......................................... 172
Part II Cancer
9
The Cell Cycle
.......................................... 179
9.1
The Cell Cycle Has Four Phases
...................... 182
9.2
Ubiquitin-Mediated Proteolysis Is a Key Part of
the Cell Cycle Machinery
............................ 183
9.3
Several Families of Activators and Inhibitors Are
Part of the Cell Cycle Engine
......................... 184
9.4
The Retinoblastoma Proteins and E2F Transcription
Factors Are Downstream Cell Cycle Effectors at the
Gl/S Transition
................................... 185
9.5
Cell Cycle Effectors at the G2/M Transition
............. 187
9.6
The SCF and APC/C Are Large Multisubunit Complexes
.. 188
9.7
Mathematical Modeling Is an Essential Tool in
Understanding Signaling Pathways and Networks
........ 189
9.8
The
Goldbeter
Model of Entry and Exit from Mitosis
..... 192
xii Contents
9.9 Multiple Positive and Negative Feedback
Regulate
the
Progression
Through the Cell Cycle
................... 194
9.10
Multisite Phosphorylation Helps Ensure the Correct
Ordering of Events
................................ 196
9.11
Traversing the Cell Cycle with the APC and SCF
........ 196
Further Reading
......................................... 197
10
Cell Cycle Checkpoints and
DNA
Damage Repair
............... 201
10.1
The Gl/S Checkpoint Pathway
...................... 202
10.2
Formation of IRIFs and Activation of ATM
........... 203
10.3
Mediators Amplify the ATM Signal
.................. 205
10.4
Intra-S Phase and G2/M Checkpoints
................. 206
10.5
Formation of SDSCs and Activation of ATR
........... 207
10.6
Structure and Posttranslational Modifications of
Checkpoint Proteins
............................... 208
10.7
p53 Structure and Function
......................... 210
10.8
Restoration of p53 Function by Second-Site
Suppressors
...................................... 212
10.9
Special Domains Mediate Protein-Protein Interactions
and Chromatin Binding by Proteins that Function
at the Apex of the Checkpoint and Repair Pathways
..... 213
10.10
Base Excision Repair
.............................. 214
10.11
Nucleotide Excision Repair
......................... 216
10.12
Mismatch Repair
................................. 216
10.13
Repair Proteins Diffuse Laterally in One-Dimension
Along
DNA..................................... 217
10.14
There Are Two Double-StrandBreak Repair
Systems
......................................... 218
10.15
The
Mrel
l-RadőO-Nbsl
(MRN)
Complex Is
Involved in
DNA
Damage Sensing, Signaling,
and Repair
...................................... 220
10.16
Completing the Repair and Terminating the
Checkpoint
...................................... 221
Further Reading
......................................... 222
11
Apoptosis and Senescence
.................................. 227
11.1
Pathways to Apoptosis
-
Extrinsic and Intrinsic
......... 228
11.2
Bcl2 Proteins Mediate the Apoptotic Balance
........... 230
11.3
Sequestration and Release of Cytochrome
с
............ 232
11.4
Damage-Induced Apoptosis via p53 Transcription
and Mitochondrial Actions
......................... 233
11.5
Cells That Are Healthy Do Not Have an Unlimited
Capacity to Divide
................................ 234
11.6
Telomere Structure and Capping Proteins
.............. 234
Contents xiii
11.7
Cancer
Cells Increase Their Production of Telomerase,
an Enzyme That Immortalizes the Cells
................ 235
11.8
Regulation of
Replicative
Senescence by p53 and pRb
.... 236
11.9 DNA
Damage and Oncogene-Induced Senescence
....... 237
11.10
A Model or Two of Oncogene-Induced Stress
........... 238
11.11
p53 Undergoes Posttranslational Modifications
Including Phosphorylation, Acetylation, and
Ubiquitination at Multiple Sites
...................... 240
11.12
Heterochromatin Formation Provides a Route to
Oncogene-Induced Senescence
....................... 241
11.13
The Retinoblastoma Protein Helps Establish the
Senescent State by Mediating Heterochromatin
Formation
....................................... 243
Further Reading
......................................... 244
12
Epigenetics
............................................. 249
12.1
Nucleosomes and Chromatin Structure
................ 250
12.2
Epigenetic Marks
................................. 251
12.3 DNA Methylation................................ 253
12.4
Polycomb and Trithorax Group Proteins
.............. 254
12.5
Histone Acetylation and Deacetylation
................ 254
12.6
Histone Methylation and Demethylation
............... 255
12.7
Reading Out Histone Marks by Recognition Modules
.... 256
12.8
Cooperative Actions by Histone Modification
Enzymes and
DNA Methyltransferases
Can Silence
Genes and Lead to Cancer
.......................... 259
12.9
Recently Discovered Small Noncoding RNAs (ncRNAs)
Regulate Gene Expression
.......................... 260
12.10
Atomic-Level Studies of Dicer and
Slicer
Provide
Crucial Insights into ncRNA Function
................ 262
12.11
MicroRNAs and Cancer
............................ 264
12.12
Induced Pluripotent Stem Cells
...................... 266
Further Reading
......................................... 267
13
Tumor Growth
.......................................... 271
13.1
Growth and Survival Signaling Pathways
.............. 271
13.2
Receptor Activation Leads to Recruitment of Molecular
Adaptors to Docking Sites
.......................... 273
13.3
Ras
and Other Small GTPases Link Adaptors to
Downstream Signaling Elements
..................... 275
13.4
Many of the Growth Signaling Proteins Function as
Oncogenes
....................................... 276
13.5
MAP Kinase Signaling Modules
..................... 278
13.6
The MAP Kinase Modules and Their Substrates
Function as Dynamical Circuits
...................... 280
xiv Contents
13.7 Active and
Inactive Conformations
of
Protein
Kinases.
... 281
13.8
Oncogene
Addiction
............................... 282
13.9
Target-Based
Anticancer
Therapies
................... 283
13.10
Мус
Protein Structure and Function
.................. 284
13.11
Phosphorylation and Polyubiquitination Sculpt
Мус
-Mediated Gene Transcription
................... 285
13.12
Regulation of Cellular Growth by
Ras, Erk,
and
Мус
___ 286
13.13
Regulation of Cellular Proliferation by
Мус
............ 287
Further Reading
......................................... 288
14
Tumor Metabolism
....................................... 291
14.1
The Central Growth Network of the Cell Is
Organized About the mTOR Cassette
................. 292
14.2
AMPK Supplies a Gating Signal Indicative of
Energy Balance
................................... 293
14.3
Cells Halt Growth in Response to Hypoxia and Other
Cellular Stresses
.................................. 293
14.4
Regulation of Cell Growth by
Amino
Acid Starvation
Signaling to mTOR
................................ 295
14.5
Regulation of the Translation Initiation Complex
by mTOR
....................................... 296
14.6
Starvation and Autophagy
.......................... 298
14.7
p53 Modulation of Metabolism Is One of Its Barrier
Functions
....................................... 300
14.8
The PTEN Tumor Suppressor Acts at the Plasma
Membrane and in the Nucleus
....................... 302
14.9
Mutations and Disturbed
Redox
Balance Deactivate
PTEN
.......................................... 303
14.10
HIF Transcription Factors Sense and Respond to
Low Oxygen Conditions
............................ 304
14.11
HIFs Regulate Cellular Metabolism and Drive the
Glycolytic Shift
................................... 306
14.12
Hexokinase II and
Akt
Drive the Glycolytic Shift
and Prevent Apoptosis in Tumors
.................... 307
Further Reading
......................................... 309
15
Metastasis
............................................. 313
15.1
Tumor Growth and Metastasis Are Community Affairs
... 314
15.2
Macrophages
and
Fibroblasts
Direct Invasion
and
Intra
vasation.................................
316
15.3
The SDF-1/CXCR4 Axis Is a Central Participant in
Metastasis
....................................... 317
15.4
Focal Adhesions and Metastasic Migration
............. 318
15.5
Receptor Cooperativity and Src Signaling
.............. 320
15.6
The Transforming Growth
Factor-ß
Pathway
........... 322
Contents xv
15.7 TGF-ß
Promotes Cytostasis
......................... 325
15.8
The Wnt Pathway
................................. 326
15.9
The Epithelial to Mesenchymal Transition
............. 327
15.10 MicroRNAs and Transcription
Repressore
Jointly
Regulate
E-Cadherin Expression..................... 329
15.11 MicroRNAs
Act as Metastasis
Repressore
and Activators
................................... 331
15.12
Stem Cells and Cancer Stem Cells
.................... 331
15.13
Changing Views About Metastatic Spread
.............. 332
15.14
The Notch Pathway
............................... 333
15.15
The Hedgehog Pathway in
Drosophila
................. 335
15.16
The Hedgehog Pathway in Mammals
................. 336
15.17
Bone Metastasis Is a Seed-and-Soil Exemplar
........... 338
Further Reading
......................................... 339
Part III Neurodegeneration
16
Protein Folding, Misfolding, and Aggregation
.................. 345
16.1
Proteins Spontaneously Fold into Their Native
State Based Solely on Their Primary
Amino
Acid Sequence
.................................... 348
16.2
Protein Folding Can Be Described in Terms of an
Energy Landscape Dominated by a Folding Funnel
...... 349
16.3
Some Landscapes Are Smooth While Others
Are Rugged
...................................... 351
16.4
Proteins, Especially Those Involved in Signaling, Often
Fold into Nonglobular, Extended Conformations
........ 352
16.5
Dialysis-Related Amyloidosis Is Brought on by Partial
Unfolding and Aggregation of
ß-2 Microglobulin........ 354
16.6
β
Cell Failure and Amyloid Formation in Type
2
Diabetes Is Brought on by Amylin Misfolding
and Aggregation
.................................. 357
16.7
Some Proteins Have Native States That Are Metastable
and Not at a Global Minimum in the Free Energy
....... 357
16.8 ß-Sheet
Conformational
Variations Underlie the Prion
Strains and Disease Potential
........................ 358
16.9
Strains and Transmissibility
......................... 361
16.10
General Observations on How Proteins Fold into
Alternative Disease-Causing Structures Characterized
by
Cross-ß-Sheets................................. 362
Further Reading
......................................... 364
17
Alzheimer s Disease
...................................... 369
17.1
Generation of the Amyloid
β
Protein
.................. 370
17.2
Removal Through Degradation and Clearance
.......... 373
xvi Contents
17.3
Folding Physics, Metal Homeostasis, and
Redox
Chemistry
....................................... 375
17.4
Normal Physiological Function of the
Aß
Protein
at the Synapse
.................................... 376
17.5
Action of the
Aß
Oligomers
at the Synapse
-
Aberrant
LTD
........................................... 377
17.6
The Local
Microenvironment
Contains Neurons,
Astrocytes, and Microglia
.......................... 379
17.7
Microglia Respond to Amyloid Plaque Buildup by
Mounting an Inflammatory Response
................. 380
17.8
Inflammatory and Synaptic Cytokines Are Released
by Microglia and Astrocytes
......................... 382
17.9 Tau Hyperphosphorylation
and Formation of
the Tangles
...................................... 384
Further Reading
......................................... 387
18
Chaperones, Endoplasmic Reticulum Stress, and the Unfolded
Protein Response
........................................ 391
18.1
The Cellular Complement of Molecular Chaperones
...... 392
18.2
Hsp70 Structure and Function
....................... 393
18.3
Hsp90 Structure and Function
....................... 394
18.4
Heat Shock Factor
1
Is a Master Regulator of Protein
Homeostasis
..................................... 396
18.5
Folding, Processing, and Maturation of Membrane
and Secreted Proteins
.............................. 397
18.6
N-Linked Glycan Processing
........................ 399
18.7
The Unfolded Protein Response
...................... 401
18.8
ERAD
and the Sec61 Translocon
.................... 404
18.9
The p97 Motor Protein Is a Molecular Chaperone
Required for
ERAD
............................... 405
Further Reading
......................................... 407
19
Parkinson s Disease
...................................... 411
19.1
a-Synuclein Is a Presynaptic Protein
.................. 414
19.2
Abnormalities and
Toxicity
Result from a-Synuclein
Misfolding and Aggregation
......................... 414
19.3
Oxidative Damage Is a Cause of a-Synuclein
Aggregation and PD
............................... 415
19.4
Parkin Is an E3 Ubiquitin
Ligase
..................... 416
19.5
Protein Carbonylation and UCH-L1
.................. 417
19.6
PINK1 Is a Neuroprotective Serine/Threonine Kinase
.... 417
19.7
DJ-1 Protects Against Oxidative Stress
................ 418
19.8
LRRK2 Is a ROCO Family Member and Mutations
in This Protein Are Most Strongly Associated with PD
... 419
19.9
Htr
Аг/Оті
Removes Misfolded Proteins
.............. 420
Contents xvii
19.10
The Pathway Is Illuminated
......................... 421
19.11
Proteasome Organization
........................... 422
19.12
Cellular Garbage Collection and the Aggresomal
-
Autophagic Railway
............................... 424
19.13
Histone Deacetylase
6
Mediates Transport Along the
Disposal Railway
................................. 425
Further Reading
......................................... 426
20
Huntington s Disease and Amyotrophic Lateral Sclerosis
......... 431
20.1
Huntington s Disease Is an Expanded PolyQ
Repeat Disorder
.................................. 432
20.2
The Structure of the Huntingtin Protein Is That of a
Multipurpose Signaling Organizer
.................... 434
20.3
Synaptic Terminal Interactions Occur
................. 434
20.4
Impaired Fast Axonal Transport Happens
............. 436
20.5
Zippers, Aggregation, Fibrils, Inclusion Body Formation,
and
Toxicity
..................................... 436
20.6
The Ubiquitin-Proteasome System Regulates
Synaptic Transmission and This Function Is Impaired
by Mutant Htt
................................... 438
20.7
Impaired Transcription:
СВР
and PGC-
1 -
and
Mitochondrial Dysfunction
......................... 439
20.8
Structure and Folding of the
Superoxide Dismutase
Protein
SODI
.................................... 440
20.9
SODI
Mutations and Aggregation
................... 441
20.10
Impaired Fast Axonal Transport and Retraction of
Axons
from Synapses
.............................. 442
20.11
A Model for Amyotrophic Lateral Sclerosis
............ 443
20.12
Acceleration of
ALS
Through Interactions Between
Neurons and Other Cellular Residents of Its
Microenvironment................................ 444
20.13
PolyQs, Mutant
SODI,
and Impaired
ERAD
........... 446
20.14
Mutations in Genes Other Than That for SOD
1
Can Cause fALS
.................................. 447
20.15
Interlocking Signaling Networks Underlie Health
and Disease
...................................... 449
Further Reading
......................................... 450
Index
..................................................... 455
Biological and Medical Physics,
Biomédical
Engineering
M. Beckerman
Cellular Signaling in Health and Disease
In todays world, three great classes of non-infectious diseases
-
the metabolic
syndromes (such as type
2
diabetes and atherosclerosis), the cancers, and the
neurodegenerative
disorders
-
have risen to the fore. These diseases, all asso¬
ciated with increasing age of an individual, have proven to be remarkably
complex and difficult to treat. This is because, in large measure, when the
cellular signaling pathways responsible for maintaining homeostasis and
health of the body become dysregulated, they generate equally stable disease
states. As a result the body may respond positively to a drug, but only for a
while and then revert back to the disease state. Cellular Signaling in Health and
Disease summarizes our current understanding of these regulatory networks
in the healthy and diseased states, showing which molecular components
might be prime targets for drug interventions. This is accomplished by pre¬
senting models that explain in mechanistic, molecular detail how a particular
part of the cellular signaling web operates properly in health and improperly
in disease.
The stability of the health- and disease-associated states is dynamic and
supported by multiple feedback loops acting positively and negatively along
with linkages between pathways. During the past few years an ongoing series
of important discoveries have been made that advance our understanding of
how the body works and may guide us on how to better deal with these
diseases. These include the discovery of chronic inflammation as a causal
factor in all of these disease classes, the appearance of reactive oxygen species
as a messenger molecule that can act both positively and negatively, the
propensity of proteins to misfold into aggregation- and disease-prone forms,
and the rise of epigenetics including the emergence of small non-coding
RNA
with important regulatory functions out of the so-called
junk RNA.
Chapters are devoted to each of these classes of findings with additional
details integrated into the chapters dealing directly with the diseases. The
connections responsible for maintaining stability are explored in depth.
|
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| dewey-sort | 3571.7 14 |
| dewey-tens | 570 - Biology |
| discipline | Biologie |
| format | Book |
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| id | DE-604.BV035629980 |
| illustrated | Illustrated |
| indexdate | 2024-07-09T21:41:58Z |
| institution | BVB |
| isbn | 9780387981727 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-017684955 |
| oclc_num | 310399984 |
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| owner | DE-355 DE-BY-UBR DE-11 |
| owner_facet | DE-355 DE-BY-UBR DE-11 |
| physical | XVII, 470 S. zahlr. Ill., graph. Darst. |
| publishDate | 2009 |
| publishDateSearch | 2009 |
| publishDateSort | 2009 |
| publisher | Springer |
| record_format | marc |
| series2 | Biological and medical physics, biomedical engineering |
| spelling | Beckerman, Martin Verfasser aut Cellular signaling in health and disease Martin Beckerman Dordrecht [u.a.] Springer 2009 XVII, 470 S. zahlr. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Biological and medical physics, biomedical engineering Cellular signal transduction Metabolic Syndrome X metabolism Neoplasms metabolism Neurodegenerative Diseases metabolism Pathology, Cellular Signal Transduction physiology Zellkommunikation (DE-588)4136131-3 gnd rswk-swf Zellkommunikation (DE-588)4136131-3 s b DE-604 Digitalisierung UB Regensburg application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=017684955&sequence=000003&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis Digitalisierung UB Regensburg application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=017684955&sequence=000004&line_number=0002&func_code=DB_RECORDS&service_type=MEDIA Klappentext |
| spellingShingle | Beckerman, Martin Cellular signaling in health and disease Cellular signal transduction Metabolic Syndrome X metabolism Neoplasms metabolism Neurodegenerative Diseases metabolism Pathology, Cellular Signal Transduction physiology Zellkommunikation (DE-588)4136131-3 gnd |
| subject_GND | (DE-588)4136131-3 |
| title | Cellular signaling in health and disease |
| title_auth | Cellular signaling in health and disease |
| title_exact_search | Cellular signaling in health and disease |
| title_full | Cellular signaling in health and disease Martin Beckerman |
| title_fullStr | Cellular signaling in health and disease Martin Beckerman |
| title_full_unstemmed | Cellular signaling in health and disease Martin Beckerman |
| title_short | Cellular signaling in health and disease |
| title_sort | cellular signaling in health and disease |
| topic | Cellular signal transduction Metabolic Syndrome X metabolism Neoplasms metabolism Neurodegenerative Diseases metabolism Pathology, Cellular Signal Transduction physiology Zellkommunikation (DE-588)4136131-3 gnd |
| topic_facet | Cellular signal transduction Metabolic Syndrome X metabolism Neoplasms metabolism Neurodegenerative Diseases metabolism Pathology, Cellular Signal Transduction physiology Zellkommunikation |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=017684955&sequence=000003&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=017684955&sequence=000004&line_number=0002&func_code=DB_RECORDS&service_type=MEDIA |
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