Abstract
Parkinson’s disease (PD) is the most common age-related motoric neurodegenerative disease initially described in the 1800’s by James Parkinson as the ‘Shaking Palsy’. Loss of the neurotransmitter dopamine was recognized as underlying the pathophysiology of the motor dysfunction; subsequently discovery of dopamine replacement therapies brought substantial symptomatic benefit to PD patients. However, these therapies do not fully treat the clinical syndrome nor do they alter the natural history of this disorder motivating clinicians and researchers to further investigate the clinical phenotype, pathophysiology/pathobiology and etiology of this devastating disease. Although the exact cause of sporadic PD remains enigmatic studies of familial and rare toxicant forms of this disorder have laid the foundation for genome wide explorations and environmental studies. The combination of methodical clinical evaluation, systematic pathological studies and detailed genetic analyses have revealed that PD is a multifaceted disorder with a wide-range of clinical symptoms and pathology that include regions outside the dopamine system. One common thread in PD is the presence of intracytoplasmic inclusions that contain the protein, α-synuclein. The presence of toxic aggregated forms of α-synuclein (e.g., amyloid structures) are purported to be a harbinger of subsequent pathology. In fact, PD is both a cerebral amyloid disease and the most common synucleinopathy, that is, diseases that display accumulations of α-synuclein. Here we present our current understanding of PD etiology, pathology, clinical symptoms and therapeutic approaches with an emphasis on misfolded α-synuclein.
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- AAV:
-
Adeno-associated viral vectors
- Ab:
-
Amyloid beta
- AchE-I:
-
Acetylcholinesterase inhibitors
- AAAD:
-
Aromatic amino acid decarboxylase
- AD:
-
Alzheimer’s disease
- ANS:
-
Autonomic nervous system
- CBD:
-
Corticobasal degeneration
- CNS:
-
Central nervous system
- COMT:
-
Catechol-O-methyltransferase
- CSF:
-
Cerebrospinal fluid
- DAT:
-
Dopamine transporter
- DBS:
-
Deep brain stimulation
- DDC:
-
DOPA decarboxylase
- DLBD:
-
Diffuse Lewy body disease
- EDS:
-
Excessive daytime sleepiness
- ET:
-
Essential tremor
- GAD:
-
Glutamic acid decarboxylase
- GDNF:
-
Glial-derived neurotrophic factor
- GI:
-
Gastrointestinal
- GPe:
-
Globus pallidus external
- GPi:
-
Globus pallidus internal
- GU:
-
Genitourinary
- GWA:
-
Genome wide association
- H&E:
-
Hematoxylin and eosin
- HLA:
-
Human leukocyte antigen
- HSF1:
-
Heat shock transcription factor 1
- 5-HT:
-
5-hydroxytryptamine
- H&Y:
-
Hoehn and Yahr
- IV:
-
Intravenous
- LBD:
-
Lewy body dementia
- L-DOPA:
-
Levodopa
- MAPT:
-
Microtubule associated protein tau
- MCI:
-
Mild cognitive impairment
- MPP+:
-
1-methyl-4-phenylpyridinium
- MPTP:
-
1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine
- MRI:
-
Magnetic resonance neuroimaging
- MSA:
-
Multiple system atrophy
- NBIA 1:
-
Neurodegeneration with brain iron accumulation type 1
- NMDA:
-
N-methyl-D-aspartate
- NMS:
-
Non-motor symptoms
- OH:
-
Orthostatic hypotension
- PD:
-
Parkinson’s disease
- PD-D:
-
Parkinson’s disease dementia
- PDRP:
-
Parkinson’s disease-related profile
- PET:
-
Positron emission tomography
- PGC-1a:
-
Proliferator-activated receptor gamma coactivator 1-alpha
- PPAR-g:
-
Peroxisome proliferator-activated receptor-gamma
- PPN:
-
Pedunculopontine nucleus
- PSP:
-
Progressive supranuclear palsy
- PTEN:
-
Phosphatase and tensin homolog
- PTX3:
-
Pentraxin 3
- QOL:
-
Quality of life
- RBD:
-
Rapid eye movement behavior sleep disorder
- REM:
-
Rapid eye movement
- ROS:
-
Reactive oxygen species
- ScFvs:
-
Single chain antibodies
- SN:
-
Substantia nigra
- SNP:
-
Single nucleotide polymorphism
- SNpc:
-
Substantia nigra pars compacta
- SNr:
-
Substantia nigra reticulata
- SSRI:
-
Selective serotonin reuptake inhibitor
- SNRI:
-
Serotonin and norepinephrine reuptake inhibitor
- STN:
-
Subthalamic nucleus
- SWEDD:
-
Scans without evidence of dopamine denervation
- TZD:
-
Thiazolidinediones
- UPDRS:
-
Unified Parkinson disease rating scale
- ViM:
-
Ventral intermediate nucleus of the thalamus
- VMAT2:
-
Vesicular monoamine transporter type 2
- VTA:
-
Ventral tegmental area
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Portions of this work were supported by NIEHS (R01ES014470; KMZ).
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Mhyre, T.R., Boyd, J.T., Hamill, R.W., Maguire-Zeiss, K. (2012). Parkinson’s Disease. In: Harris, J. (eds) Protein Aggregation and Fibrillogenesis in Cerebral and Systemic Amyloid Disease. Subcellular Biochemistry, vol 65. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5416-4_16
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