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E-raamat: Recent Advances in Parkinson's Disease

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  • Sari: Progress in Brain Research
  • Ilmumisaeg: 02-Apr-2020
  • Kirjastus: Elsevier Science Ltd
  • Keel: eng
  • ISBN-13: 9780444642615
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  • Formaat: PDF+DRM
  • Sari: Progress in Brain Research
  • Ilmumisaeg: 02-Apr-2020
  • Kirjastus: Elsevier Science Ltd
  • Keel: eng
  • ISBN-13: 9780444642615

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Recent Advances in Parkinson´s Disease Research, Volume 252, represents a follow-up on two previous volumes presented in the Progress in Brain Research series, Volumes 193 and 193, both published in 2010. It contains a collection of overview articles written by leading researchers in Parkinson's, discussing the most important advances made in basic, translational and clinical research. Topics of note in this new release include What can we learn from iPS cell models of PD, What can we learn from animal models of PD , Molecular basis of selective neuronal vulnerability in PD, Role of innate and adaptive immunity in Parkinson´s disease, and much more.
Contributors v
Preface: The evolving scenario of Parkinson's research xix
Part I Basic science
Chapter 1 What we can learn from iPSC-derived cellular models of Parkinson's disease
1(26)
Maria Claudia Caiazza
Charmaine Lang
Richard Wade-Martins
1 Introduction
4(1)
2 Establishment of iPSC technology and methods of differentiation into DAns
5(2)
2.1 Establishment of induced pluripotent stem cells
5(1)
2.2 Differentiation into DAns
6(1)
3 iPSC-derived neurons for disease modeling
7(7)
3.1 Endoplasmic reticulum stress
10(1)
3.2 Protein trafficking and degradation deficits
11(1)
3.3 Mitochondrial defects and oxidative stress
12(2)
3.4 Alterations in calcium homeostasis
14(1)
4 iPSC-derived glial cells for disease modeling
14(1)
5 Co-culture systems, 3D cultures and organoids for disease modeling
15(2)
6 iPSC-derived neurons for cell-based treatments
17(1)
7 Limitations of iPSC-based models
17(1)
8 Future applications
18(1)
9 Conclusions
19(1)
Acknowledgments
20(1)
References
20(7)
Chapter 2 Animal models for preclinical Parkinson's research: An update and critical appraisal
27(34)
M. Angela Cenci
Anders Bjorklund
1 Introduction
28(1)
2 Models in different species
28(1)
3 The importance of nigrostriatal dopaminergic degeneration
29(1)
4 6-Hydroxydopamine
30(2)
5 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
32(1)
6 Environmental toxicants
33(2)
6.1 Rotenone
33(1)
6.2 Paraquat
34(1)
7 Proteasome inhibitors
35(1)
8 Alpha-synuclein models
36(9)
8.1 The AAV-&alplha;-synuclein model
36(2)
8.2 The PFF inoculation model
38(3)
8.3 Combined AAV-PFF α-synuclein models
41(1)
8.4 Transgenic α-synuclein overexpressing mice
42(3)
9 Other genetic models of PD
45(2)
10 Concluding remarks
47(1)
Acknowledgments
48(1)
References
48(13)
Chapter 3 Selective neuronal vulnerability in Parkinson's disease
61(30)
Patricia Gonzalez-Rodriguez
Enrico Zampese
D. James Surmeier
1 Introduction
62(1)
2 Cell autonomous determinants of vulnerability
63(5)
3 Non-cell autonomous determinants and ct-SYN
68(3)
4 Toward a consensus view of PD pathogenesis
71(2)
References
73(18)
Chapter 4 Mechanisms of alpha-synuclein toxicity: An update and outlook
91(40)
Ines Caldeira Bras
Mary Xylaki
Tiago Fleming Outeiro
1 Introduction
93(2)
2 Parkinson's disease: Clinical features and genetic factors
95(1)
3 Other synucleinopathies
96(1)
3.1 Dementia with Lewy bodies
96(1)
3.2 Multiple system atrophy
96(1)
3.3 Pure autonomic failure
97(1)
3.4 REM sleep behavior disorder
97(1)
3.5 Genetic factors in other synucleinopathies
97(1)
4 Alpha-synuclein
97(5)
4.1 Alpha-synuclein physiology
97(1)
4.2 Protein sequence
98(2)
4.3 Tertiary and quaternary structure of aSyn
100(1)
4.4 The effect of PD-associated mutations in aSyn
101(1)
4.5 Post-translational modifications
101(1)
5 Alpha-synuclein pathology in the synapse
102(1)
6 aSyn pathology in mitochondria
103(1)
7 aSyn pathology in the ER-Golgi compartments
104(3)
7.1 Degradation and clearance of aSyn
105(1)
7.2 aSyn pathology and the cytoskeleton
106(1)
7.3 Effects of aSyn in the nucleus
106(1)
8 Spreading of aSyn pathology
107(3)
9 The interplay between aSyn and the microbiome
110(1)
10 Inflammation
110(1)
11 Conclusions and outlook
111(1)
Acknowledgments
112(1)
References
112(19)
Chapter 5 The role of glia in Parkinson's disease: Emerging concepts and therapeutic applications
131(38)
Katarzyna Z. Kuter
M. Angela Cenci
Anna R. Carta
1 Glial cells in PD: A brief introduction
132(6)
1.1 Physiopathological functions of microglia
133(3)
1.2 Physiopathological functions of astroglia
136(2)
2 Role of glia in the neurodegenerative process
138(4)
2.1 Microglia
138(2)
2.2 Astroglia
140(2)
3 Role of glia in dopamine replacement therapy
142(3)
3.1 Role of glia in the uptake and metabolism of L-DOPA
142(1)
3.2 Role of glia in L-DOPA-induced dyskinesia
143(1)
3.3 Gliovascular mechanisms in L-DOPA-induced dyskinesia
144(1)
4 Therapeutic applications
145(7)
4.1 Microglia as a therapeutic target for disease-modification
145(4)
4.2 Astroglia as an effector of disease-modifying treatments
149(1)
4.3 Glial-based cell replacement therapies for PD
150(1)
4.4 Targeting glial mechanisms to treat L-DOPA-induced dyskinesia
151(1)
5 Concluding remarks
152(1)
References
152(17)
Chapter 6 Innate and adaptive immune responses in Parkinson's disease
169(48)
Aubrey M. Schonhoff
Gregory P. Williams
Zachary D. Wallen
David G. Standaert
Ashley S. Harms
1 Introduction
169(2)
2 PD as a systemic and heterogeneous disease
171(1)
3 Innate immune system
172(3)
4 Adaptive immune system
175(3)
5 CNS inflammation in human PD
178(3)
5.1 CNS parenchyma
178(2)
5.2 Cerebrospinal fluid
180(1)
6 Peripheral inflammation in PD
181(3)
6.1 Blood
181(2)
6.2 Gastrointestinal tract, enteric nervous system, and the microbiome
183(1)
7 The immuno-genetics of PD
184(3)
7.1 SNCA
184(1)
7.2 HLA
185(1)
7.3 LRRK2
185(1)
7.4 PINK] and Parkin
186(1)
8 Immune modulation and risk of Parkinson's disease
187(1)
9 Inflammation in murine models of PD
187(6)
9.1 Neurotoxin-based animal models of PD
188(2)
9.2 α-syn based animal models of PD
190(3)
10 Conclusions and key questions
193(6)
10.1 Key question 1: What is the role of a-syn in activating the immune system?
193(3)
10.2 Key question 2: Is Parkinson's disease caused by an immune response that originates in the gut?
196(1)
10.3 Key question 3: What is the role of microglia in Parkinson's disease?
197(1)
10.4 Key question 4: How do t cells contribute to the pathobiology of Parkinson's disease?
198(1)
10.5 Conclusion
199(1)
References
199(18)
Chapter 7 Pathways of protein synthesis and degradation in PD pathogenesis
217(54)
Rebekah G. Langston
Mark R. Cookson
1 Introduction
217(1)
2 Protein synthesis
218(8)
2.1 Transcription
218(3)
2.2 Translation
221(3)
2.3 Post-translational modification
224(2)
3 Protein degradation
226(16)
3.1 Proteasome
226(5)
3.2 Lysosome
231(6)
3.3 Endoplasmic reticulum
237(5)
4 Summary
242(1)
Acknowledgment
242(1)
References
242(29)
Chapter 8 Endosomal sorting pathways in the pathogenesis of Parkinson's disease
271(36)
Lindsey A. Cunningham
Darren J. Moore
1 Genetics lead the way to understanding Parkinson's disease pathogenesis
272(1)
2 Role of familial PD genes in endosomal sorting pathways
273(12)
2.1 The endolysosomal system
273(2)
2.2 Vacuolar protein sorting-associated protein 35 (VPS35)
275(4)
2.3 Leucine-rich repeat kinase 2 (LRRK2)
279(4)
2.4 SNCA/a-synuclein
283(2)
3 Emerging endosomal evidence in PD: Synaptic vesicle endocytosis and Rab GTPases
285(5)
3.1 Synaptic vesicle endocytosis (SVE)
285(3)
3.2 Rab GTPases
288(2)
4 Conclusion and future directions
290(1)
Acknowledgments
291(1)
References
291(16)
Chapter 9 New players in basal ganglia dysfunction in Parkinson's disease
307(22)
Sara Meoni
Rubens Gisbert Cury
Elena Moro
1 Introduction
307(1)
2 The spinal cord
308(2)
2.1 Stimulation of the spinal cord
308(2)
3 The pedunculopontine nucleus
310(1)
3.1 Stimulation of the pedunculopontine nucleus area
311(1)
4 The substantia nigra pars reticulata
311(1)
4.1 Stimulation of the substantia nigra pars reticulata
311(1)
5 The retina
312(2)
6 The superior colliculus
314(1)
7 The cerebellum
315(1)
8 The parabrachialis nucleus
316(1)
9 The nucleus basalis of Meynert
316(1)
9.1 Stimulation of the nucleus basalis of Meynert
317(1)
10 Conclusions
317(1)
References
318(11)
Part II Translational therapeutics
Chapter 10 Prodromal PD: A new nosological entity
329(28)
Eva Schaeffer
Ronald B. Postuma
Daniela Berg
1 Introduction
331(1)
2 Pathophysiology: Current concepts
332(1)
3 Markers
333(12)
3.1 The research criteria for prodromal PD
334(1)
3.2 Risk markers
335(3)
3.3 Prodromal markers
338(7)
4 Conclusion
345(1)
References
346(11)
Chapter 11 The gut microbiome in Parkinson's disease: A culprit or a bystander?
357(94)
Ali Keshavarzian
Phillip Engen
Salvatore Bonvegna
Roberto Cilia
1 Gut microbiota in healthy subjects
358(8)
1.1 Introductions and definitions
358(1)
1.2 Microbial diversity: Definition and significance
359(3)
1.3 Factors modulating gut microbiota
362(3)
1.4 "Microbiota for dummies": Disentangling methods for studying gut microbiota
365(1)
2 Gut microbiota in the pathogenesis of Parkinson's disease
366(11)
2.1 Gut microbiota and neuroinflammation
367(4)
2.2 Metabolic mediators: The role of SCFAs in PD
371(3)
2.3 Is PD associated with a "leaky gut"?
374(3)
2.4 The role of virus (phageome)
377(1)
3 Genetic factors
377(4)
3.1 Twin studies
377(1)
3.2 PD-causing genes and neuroinflammation
378(3)
3.3 Genes involved in the modulation of immune response to microbiota
381(1)
4 Environmental factors/lifestyle habits modulating gut microbiota
381(4)
4.1 Environmental factors
381(2)
4.2 Lifestyle habits
383(2)
5 Upper gut microbiota (nasal, stomach and small intestine) and PD
385(1)
5.1 Nasal and oral microbiota
385(1)
5.2 Stomach: Helicobacter pylori and response to Levodopa
385(1)
5.3 Small intestine: The role of bacterial overgrowth (SIB0)
386(1)
6 Lower gut microbiota (colonic) and PD
386(34)
6.1 Preclinical studies
386(12)
6.2 Clinical studies
398(22)
7 Are gut microbiota changes a cause or a consequence of Parkinson's disease?
420(3)
7.1 Relationship between gut microbiota and PD clinical features
421(1)
7.2 Interaction between gut microbiota and PD medications
421(2)
8 Interventions on gut microbiota as potential disease modifying strategies?
423(1)
9 Does PD start in the gut?
424(3)
9.1 A pathogen passes the gastrointestinal mucosa
425(1)
9.2 a-Syn aggregates in post-ganglionic ENS terminals
425(1)
9.3 Does a-syn pathology spread from gut to brain?
425(2)
9.4 How does a-syn spread throughout the CNS?
427(1)
9.5 Do Lewy bodies induce neuronal death?
427(1)
10 Conclusions
427(1)
Acknowledgments
428(1)
References
428(19)
Further Reading
447(4)
Chapter 12 Novel approaches to counter protein aggregation pathology in Parkinson's disease
451(42)
Simon R.W. Stott
Richard K. Wyse
Patrik Brundin
1 Introduction
451(4)
2 Immunotherapy
455(4)
2.1 Immunotherapy-Passive
456(2)
2.2 Immunotherapy-Active
458(1)
3 Small molecule anti-aggregates
459(2)
4 Lysosomal-based enhancers
461(3)
5 Autophagy inducers
464(2)
6 LRRK2 inhibition
466(1)
7 Iron chelation
467(1)
8 GLP-1 agonists
468(1)
9 Preclinical developments
469(3)
9.1 β2-adrenergic receptor agonists
469(1)
9.2 Intrabodies
470(1)
9.3 PARP inhibition
470(1)
9.4 Stearoyl-CoA desaturase inhibition
471(1)
9.5 Inflammasome inhibition
471(1)
9.6 Proteasome activation
472(1)
9.7 Deubiquitinating enzymes
472(1)
10 Concluding remarks
472(2)
Acknowledgments
474(1)
Conflicts of interest
474(1)
References
474(19)
Chapter 13 Repurposing anti-diabetic drugs for the treatment of Parkinson's disease: Rationale and clinical experience
493(32)
Tom Foltynie
Dilan Athauda
1 Links between diabetes and Parkinson's disease
494(2)
2 Causation or shared patho-etiology?
496(3)
3 Anti-diabetic agents
499(1)
4 Metformin and PD
499(1)
5 Thiozolidinediones and PD
500(1)
6 Insulin as a therapy for PD
501(1)
7 GLP-1 receptor agonists, DPP-4 inhibitors and PD
502(11)
7.1 DPP4 inhibitors and PD
502(1)
7.2 Exenatide
503(1)
7.3 The rationale for using GLP-1 receptor agonists in PD
504(1)
7.4 GLP-1 in vitro
504(1)
7.5 GLP-1 in animal models
505(1)
7.6 Results of exenatide in clinical trials
506(7)
8 Which PD patients might do best on GLP-1 agonist medications?
513(1)
8.1 Dual incretin agonists
513(1)
9 Concluding remarks
514(1)
References
514(11)
Chapter 14 Basal ganglia oscillations as biomarkers for targeting circuit dysfunction in Parkinson's disease
525
Per Petersson
Andrea A. Kuhn
Wolf-Julian Neumann
Romulo Fuentes
1 Introduction
526(4)
1.1 Why circuit level pathophysiological processes are important to consider in PD
526(2)
1.2 The emergence and spreading of synchronized oscillatory activity in cortico-basal ganglia-thalamic structures in PD
528(1)
1.3 The value of translational neurophysiological biomarkers for improved treatment of PD
529(1)
2 Oscillations associated with hypokinesia
530(5)
2.1 Recordings in PD patients
530(1)
2.2 Recordings in primate models of PD
531(1)
2.3 Recordings in rodent models of PD
532(1)
2.4 Beta oscillations in neuronal networks and the role abnormal connectivity
533(1)
2.5 Utilizing beta activity for target selection and programming in DBS
534(1)
3 Oscillations related to hyperkinesia
535(4)
3.1 Oscillations associated with dystonia
535(1)
3.2 Oscillations associated with dyskinesia
536(3)
4 Oscillations at very high frequencies (>100Hz)
539(1)
5 Oscillations associated with non-motor symptoms
540(1)
6 Oscillations as biomarkers for targeting circuit dysfunction
541(3)
6.1 Oscillations as biomarkers in neuromodulation
541(2)
6.2 Oscillations as biomarkers in drug development
543(1)
7 Conclusions
544(1)
References
544
Anders Björklund is Senior Professor of neuroscience at Lund University (Sweden). His research career at Lund University spans over more than 50 years, and has resulted in a publication list that covers over 600 papers. His major achievements are in the field of cell transplantation and brain repair. He started this line of research in the mid 1970ies, based on the idea that immature neurons can be used to restore brain circuitry and promote functional recovery in animal models of neurodegenerative diseases. During this period, 1975-1985, his group pioneered this approach using cells obtained from the fetal brain. Anders and his clinical collaborators obtained permission to use tissue from aborted human fetuses in a series of open-label clinical trials in PD patients. Although the outcome of these trials has been quite variable, they have given proof-of-principle that immature dopamin neurons can survive and mature in the striatum in advanced PD patients, and restore dopamine neurotransmission in the area of the striatum re-innervated by the grafted neurons. Since the 1980ies the Lund neural transplantation program has been a leader in the development of restorative therapies in Parkinson´s disease. Current efforts at the Wallenberg Neuroscience center are focused on the development of stem cell-derived dopamine neurons for transplantation, aimed at the development of transplantable neurons derived from human pluripotent stem cells for clinical application. In a parallel line of work Anders group has explored the use of viral vector-mediated gene transfer for neuroprotection and brain repair, with the aim to develop new therapeutic approaches for Parkinson´s disease and other neurodegenerative disorders. In addition, he has pioneered the use of AAV vectors for overexpression of human -synuclein for induction of Parkinson-like neurodegeneration in the nigrostriatal system. This approach has provided a new tool for modeling of the progressive synuclein-induced disease process in animal models of PD. Angela Cenci Nilsson (author name M. A. Cenci) is Professor of Experimental Medical Research at Lund University (Sweden) where she heads the Basal Ganglia Pathophysiology Group). The groups research activities address the pathophysiology and pharmacology of Parkinsons disease (PD) and L-DOPA-induced dyskinesia using a multidisciplinary and translational approach. Current projects span a large variety of topics, including synaptic dysfunctions, dopamine receptor signaling, gliovascular-neuronal interactions, and neurorestorative treatments to enhance function and plasticity in the damaged nigrostriatal pathway.

Angela has a combined clinical-basic science background, having graduated in Medicine and specialized in Neurology at the University of Verona (Italy) before obtaining a PhD degree in Neurobiology at Lund University under the supervision of Prof. Anders Björklund. In 2002 Angela received a tenured appointment as Associate Professor at Lund University, which was followed by an appointment as Full Professor in 2008.

Angela has pioneered the development of symptomatic models of parkinsonism and L-DOPA-induced dyskinesia in rodents, and exploited these models to discover cellular mechanisms of disease and new therapeutic approaches. For these research achievements, she has received several awards (such as, the Erik K. Fernström Award for Young Promising Investigators, the Medal of Honours for Parkinson´s Research by the Swedish Parkinsons Disease Foundation, and a recent membership in the Royal Academy for the Natural Sciences, Medicine and Technology in Lund). Angela currently serves on the scientific advisory boards and steering committees of several national and international research organizations, including the Swedish National Microscopy Infrastructure, The Swedish Parkinsons Research Foundation, the Swedish Brain Foundation, the International Association for Parkinsonism and Related Disorders (IAPDR), and the International Basal Ganglia Society (IBAGS).