Handbook of Parkinson's disease mechanisms / Edited by Rosario Moratalla, Mario Gustavo Murer.

Format:

Book

Contributor:

Moratalla, Rosario, editor.

Murer, Mario Gustavo, editor.

Series:

Handbook of Behavioral Neuroscience ; Volume 35.

Handbook of Behavioral Neuroscience ; Volume 35

Language:

English

Subjects (All):

Parkinson's disease.

Neurosciences.

Physical Description:

1 online resource (1155 pages)

Place of Publication:

London : Academic Press, 2025.

Summary:

The Handbook of Parkinson's Disease Mechanisms offers an integrated overview of the fundamental research devoted to understanding its causes and mechanisms, highlighting recent advances and clinical significance.

Contents:

Front Cover

Handbook of Parkinson's Disease Mechanisms

Copyright

Contents

Contributors

Preface

Acknowledgments

1 - Cross-talk between genetic and environmental factors in Parkinson's disease

1. Introduction

2. Environmental hypothesis of Parkinson's disease

2.1 Toxin exposure and animal models

2.1.1 Paraquat (PQ)

2.1.2 Maneb

2.1.3 Dieldrin

2.1.4 Rotenone

2.1.5 Other environmental toxicants

2.2 Toxin exposure and human susceptibility to PD

2.3 Toxins and oxidative stress

2.4 Protein misfolding and inclusion formation

3. Environmental toxins and inflammation

4. Routes of environmental exposure and the pathogenesis of PD

5. Environmental toxins and genetic vulnerability

6. Summary and conclusions

References

2 - Neuromelanin: Bridging catecholamine metabolism and neurodegeneration in Parkinson's disease

1. Catecholamine metabolism in Parkinson's disease

1.1 General overview of catecholamine metabolism

1.2 Alterations in catecholamine metabolism in PD

1.3 Putative pathogenic role of dopamine oxidation in PD pathogenesis

1.3.1 O-quinone modification of proteins related to dopaminergic metabolism and synaptic release

1.3.2 O-quinones and oxidative stress

1.3.3 O-quinones and mitochondrial dysfunction

1.3.4 O-quinones and autophagy dysfunction

1.3.5 O-quinones and neuroinflammation

1.3.6 Aminochrome and 5SCDA toxicity

1.3.7 Effects of l-DOPA treatment on catecholamine oxidation

2. Neuromelanin and Parkinson's disease

2.1 NM synthesis and age-dependent accumulation

2.1.1 Biosynthesis of peripheral melanins

2.1.2 NM biosynthesis

2.1.3 NM age-dependent accumulation

2.1.4 NM function

2.2 Experimental NM models

2.2.1 In vitro NM-producing models.

2.2.2 In vivo NM-producing models

2.3 Selective vulnerability of NM-producing regions in PD

2.3.1 Anatomical and physiological features

2.3.2 Molecular signatures

2.3.3 High levels of pigmentation

2.4 Role of NM in brain aging and PD pathogenesis

2.4.1 NM in brain aging

2.4.2 Mechanisms of NM-linked neurodegeneration

3 - Rodent models for exploring the mechanisms contributing to Parkinson's disease pathophysiology

2. An overview on rodent models of PD

2.1 Pharmacological models of PD

2.2 Toxin models of PD

2.3 Nongenetic alpha-synuclein models of PD

2.4 Genetic models

2.5 Combinatorial models

3. Modeling etiology

3.1 Age

3.2 Sex

3.3 Environmental toxins

3.4 Genetics

4. Modeling the underlying pathophysiology in PD

4.1 Nigrostriatal degeneration

4.2 Extra-nigral neuronal degeneration &amp

dysfunction

4.3 Lewy pathology and α-synucleinopathy

4.4 Mitochondrial dysfunction &amp

oxidative stress

4.5 Autophagy &amp

proteasomal dysfunction

4.6 Neuroinflammation

5. Modeling the motor symptoms of PD

6. Modeling nonmotor symptoms

6.1 Sleep disturbances

6.2 Sensory abnormalities

6.3 Gastrointestinal dysfunction

6.4 Cognitive deficits: memory impairment

6.5 Depression &amp

anxiety

7. Conclusion

4 - Non-human primate models of Parkinson's disease and related synucleinopathies

1. Rationale behind modeling PD in NHPs

2. Symptomatic models: The MPTP model as the gold-standard choice

3. Neuropathological models (I): Models based on alpha-synuclein

4. Neuropathological models (II): Models based on neuromelanin

5. Concluding remarks

5 - Alpha-synuclein spreading in Parkinson's disease.

1. Evidence from human studies for α-synuclein propagation in PD

2. Experimental evidence for α-synuclein propagation

3. Seeding amplification of α-syn

4. Synuclein tissue amplification assay

5. Materials and methods

5.1 Animals and immunohistochemistry

6. Tissue amplification assay (TAA) protocol

7. Proteinase K digestion assay

8. Statistical analysis

9. Future prospects and opportunities

6 - The role of mitochondria in the pathogenesis of Parkinson's disease

2. Mitochondrial structure, function, and mtDNA

2.1 Mitochondria in neurons

2.2 Mitochondrial dysfunction in neurodegenerative disorders

3. Mitochondria dysfunction in PD: ETC impairment

4. mtDNA and nDNA related mitochondrial perturbations in PD

5. Prospects for therapeutic intervention

6. Conclusion

7 - Parkinson's disease: A chronic systemic inflammatory disorder

1. Preface

2. The immune system and the inflammatory response: An overview

2.1 Basics of the immune system

2.2 A working definition of neuroinflammation

3. Evidence of systemic neuroinflammation in PD

3.1 Innate immune cell activation

3.2 Pattern recognition receptors

3.3 Release of proinflammatory signaling molecules

3.4 Microvascular changes

3.5 Recruitment of peripheral immune cells

4. The initiating immunogenic stimuli in PD: What, where, and when

4.1 What initiates neuroinflammation in PD?

4.2 Where is neuroinflammation initiated in PD?

4.3 When is neuroinflammation initiated in PD?

5. Conclusions and future directions

8 - Transcription factor NRF2: New therapeutic approach to modify Parkinson's disease progression

1. NRF2 pathway

2. Parkinson's disease and NRF2

3. Mitochondria, NRF2, and PD

4. Relationship between oxidative stress and NRF2 in PD.

5. Ferroptosis and NRF2 in PD

6. Role of NRF2 in neuroinflammation and PD

6.1 Main players involved in neuroinflammation linked to PD: NRF2 role

6.1.1 Role of astrocytes

6.1.2 Role of microglia

6.1.3 Endothelial inflammation and blood-brain barrier permeability

6.2 NRF2 activity to contain proinflammatory responses: Multifaceted mechanisms

6.2.1 Transcriptional control of inflammation: The crossroad of NF-kB and NRF2

6.2.2 Redox control of microglial dynamics

6.2.3 Direct effects of NRF2 activity on the expression of proinflammatory genes

7. Proteostasis-NRF2 and PD

8. Pharmacologic targeting of NRF2 as a disease modifying therapy for Parkinson's disease

9. Concluding remarks

9 - Dopamine neurotransmission in Parkinson's disease

1.1 The neurobiology of dopamine release

1.2 Neuromodulators shaping dopamine release

1.3 Downstream effects of striatal dopamine neurotransmission

1.4 Evidence for early axonal dysfunction and dopamine release defects in PD patients

2. Dopamine release in animal and human-based cell models of PD

2.1 Autosomal dominant genes

2.1.1 SNCA (PARK1)

2.1.2 LRRK2 (PARK8)

2.1.3 VPS35 (PARK17)

2.2 Autosomal recessive genes with typical parkinsonism

2.2.1 PARKIN (PARK2)

2.2.2 PINK1 (PARK6)

2.2.3 DJ-1 (PARK7)

2.3 Major risk factors for Parkinson's disease

2.3.1 GBA1

3. Mechanisms of dopamine release defects

3.1 Synaptic vesicle exocytosis

3.2 Synaptic vesicle trafficking and loading

3.3 Damage to the vesicle pool

3.4 Synaptic vesicle endocytosis, recycling and dopamine reuptake

3.5 Presynaptic protein accumulation

3.6 Heteroreceptor mechanisms

4. Outstanding questions and concluding remarks

Competing interests

Acknowledgments and Funding

References.

10 - Morphological plasticity of striatal medium spiny neurons: Its potential contribution to Parkinson's disease p ...

2. Basal ganglia, dorsal striatum, and striatal neurons

3. Striatal dopamine innervation and patterns of denervation in PD

4. Morphological and functional plasticity of MSNs in PD

4.1 Spine loss on direct versus indirect striatofugal MSNs in PD

4.2 Dopamine depletion, spine loss and severity of motor symptoms in PD

4.3 Functional significance of spine loss and glutamatergic synaptic plasticity in PD

4.3.1 Ultrastructural plasticity of glutamatergic axospinous synapses

4.3.1.1 Remodeling of perisynaptic astrocytes in Parkinsonism

4.4 Striatal MSNs plasticity in PD: Homeostatic or maladaptive?

5. Dendritic spine recovery on MSNs after dopamine replacement therapy

5.1 Dopaminergic therapy and l-DOPA-induced dyskinesias (LIDs)

5.2 Non-dopaminergic therapies

5.2.1 Exercise and motor training

5.2.2 Electroacupunture

5.2.3 Calcium channel inhibition

6. Striatal dopamine loss and MSNs plasticity in dystonia

6.1 l-DOPA-responsive dystonia (DRD)

6.2 DYT1 dystonia

7. Conclusions and knowledge gaps

11 - Network determinants of motor disability in Parkinson's disease

1. Classical basal ganglia circuitry model of network dysfunction in Parkinson's disease (PD)

2. The striatal circuitry-an updated view

3. Striatal adaptions and their contributions to PD motor symptoms

4. Extra-striatal adaptations and their contributions to PD motor symptoms

12 - Molecular mechanisms of l-DOPA-induced dyskinesia

2. Dopamine receptors: Critical mediators of abnormal postsynaptic signaling

3. Mechanisms and consequences of supersensitive D1 signaling in LID.

4. ERK1/2 at the crossroad of multiple signaling routes.

Notes:

Description based on publisher supplied metadata and other sources.

ISBN:

0-443-21993-1

0-443-21992-3

9780443219931

OCLC:

1551440555