Neuropathology and pathogenesis of extrapyramidal movement disorders: a critical update—I. Hypokinetic-rigid movement disorders

Jellinger, K. A.

doi:10.1007/s00702-019-02028-6

Cited by 28 publications

(27 citation statements)

References 926 publications

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“…Neuropathological studies of PSP brains have traditionally focused on changes in the brainstem, basal ganglia, and frontal lobe, providing straightforward correlations with the cardinal signs of the disease, namely supranuclear saccade slowing, parkinsonism, and frontal-type dementia. 35,36 However, recent cross-sectional and longitudinal neuroimaging studies have found small but significant amounts of atrophy in the temporal lobe of PSP patients, whereas most researchers tend to associate these changes with behavioral deficits. [37][38][39][40] Unfortunately, no previous study has attempted to link any parts of the temporal lobe with SWJs.…”

Section: Jcnmentioning

confidence: 99%

A Cortical Substrate for Square-Wave Jerks in Progressive Supranuclear Palsy

et al. 2020

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Background and Purpose Square-wave jerks (SWJs) are the most common saccadic intrusion in progressive supranuclear palsy (PSP), but their genesis is uncertain. We aimed to determine the characteristics of SWJs in PSP (the Richardson subtype) and Parkinson's disease (PD) and to map the brain structures responsible for abnormal SWJ parameters in PSP. Methods Eye movements in 12 patients with PSP, 12 patients with PD, and 12 age-matched healthy controls were recorded using an infrared corneal reflection device. The rate, mean amplitude, and velocity of SWJs were analyzed offline. Voxel-based morphometry using a 3-Tesla MRI scanner was performed to relate changes in brain volume to SWJ parameters. Results The SWJ rate was more than threefold higher in PSP patients than in both PD patients and controls (mean rates: 33.5, 10.3, and 4.3 SWJs per minute, respectively). The volumes of neither the midbrain nor other infratentorial brain regions were correlated with the SWJ rate. Instead, highly significant associations were found for atrophy in the superior, middle, and inferior temporal gyri in the PSP group. Conclusions SWJs in PSP are not mediated by midbrain atrophy. Instead, supratentorial cortical structures located mainly in the temporal lobe appear to be deeply involved in the generation of abnormally high SWJ rates in these patients. Known anatomical connections of the temporal lobe to the superior colliculus and the cerebellum might play a role in SWJ genesis.

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Section: Jcnmentioning

confidence: 99%

A Cortical Substrate for Square-Wave Jerks in Progressive Supranuclear Palsy

et al. 2020

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“…The PD-linked G2019S mutation in LRRK2 enhances α-synuclein propagation efficiency by Ras-related protein Rab-35 phosphorylation [104]. The interaction of LRRK2 and αsynuclein has been reviewed recently in detail by O Hara et al [105] Indeed, this interaction has been challenged, as post-mortem brain analyses have not shown LB in LRRK2-induced PD [105,106]. Experimental studies demonstrate that the expression of familial mutant G2019S LRRK2 does not dramatically elevate α-synuclein or neurodegeneration in neurons [107].…”

Section: Genetic and α-Synuclein-related Pathological Processes In Pdmentioning

confidence: 99%

The Nigral Coup in Parkinson’s Disease by α-Synuclein and Its Associated Rebels

Sian-Hülsmann

Riederer

2021

Cells

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The risk of Parkinson’s disease increases with age. However, the etiology of the illness remains obscure. It appears highly likely that the neurodegenerative processes involve an array of elements that influence each other. In addition, genetic, endogenous, or exogenous toxins need to be considered as viable partners to the cellular degeneration. There is compelling evidence that indicate the key involvement of modified α-synuclein (Lewy bodies) at the very core of the pathogenesis of the disease. The accumulation of misfolded α-synuclein may be a consequence of some genetic defect or/and a failure of the protein clearance system. Importantly, α-synuclein pathology appears to be a common denominator for many cellular deleterious events such as oxidative stress, mitochondrial dysfunction, dopamine synaptic dysregulation, iron dyshomeostasis, and neuroinflammation. These factors probably employ a common apoptotic/or autophagic route in the final stages to execute cell death. The misfolded α-synuclein inclusions skillfully trigger or navigate these processes and thus amplify the dopamine neuron fatalities. Although the process of neuroinflammation may represent a secondary event, nevertheless, it executes a fundamental role in neurodegeneration. Some viral infections produce parkinsonism and exhibit similar characteristic neuropathological changes such as a modest brain dopamine deficit and α-synuclein pathology. Thus, viral infections may heighten the risk of developing PD. Alternatively, α-synuclein pathology may induce a dysfunctional immune system. Thus, sporadic Parkinson’s disease is caused by multifactorial trigger factors and metabolic disturbances, which need to be considered for the development of potential drugs in the disorder.

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“…This diversity in non-motor pathology which accompanies the common striatal dopaminergic deficits in non-transgenic PD models seems to fit the human PD condition for which the work of Braak et al (2003) indicates that the neurodegenerative process could start in the peripheral nervous system, and progress towards the central nervous system in a caudal-to-rostral direction, so called bottom-up concept of propagation. However, others argue that, based on cases with intact vagal motor nucleus, the Braak staging cannot apply to all PD cases suggesting that there are different PD endophenotypes-clinical correlates (Jellinger 2019). This suggests that the neocortex may not necessarily be the final stage of bottom-up propagation.…”

Section: Selective Neuronal and Regional Toxicitymentioning

confidence: 99%

Shared cerebral metabolic pathology in non-transgenic animal models of Alzheimer's and Parkinson's disease

et al. 2020

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Parkinson's disease (PD) and Alzheimer's disease (AD) are the most common chronic neurodegenerative disorders, characterized by motoric dysfunction or cognitive decline in the early stage, respectively, but often by both symptoms in the advanced stage. Among underlying molecular pathologies that PD and AD patients have in common, more attention is recently paid to the central metabolic dysfunction presented as insulin resistant brain state (IRBS) and altered cerebral glucose metabolism, both also explored in animal models of these diseases. This review aims to compare IRBS and alterations in cerebral glucose metabolism in representative non-transgenic animal PD and AD models. The comparison is based on the selectivity of the neurotoxins which cause experimental PD and AD, towards the cellular membrane and intracellular molecular targets as well as towards the selective neurons/non-neuronal cells, and the particular brain regions. Mitochondrial damage and coexpression of insulin receptors, glucose transporter-2 and dopamine transporter on the membrane of particular neurons as well as astrocytes seem to be the key points which are further discussed in a context of alterations in insulin signalling in the brain and its interaction with dopaminergic transmission, particularly regarding the time frame of the experimental AD/ PD pathology appearance and the correlation with cognitive and motor symptoms. Such a perspective provides evidence on IRBS being a common underlying metabolic pathology and a contributor to neurodegenerative processes in representative non-transgenic animal PD and AD models, instead of being a direct cause of a particular neurodegenerative disorder.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Neuropathology and pathogenesis of extrapyramidal movement disorders: a critical update—I. Hypokinetic-rigid movement disorders

Cited by 28 publications

References 926 publications

A Cortical Substrate for Square-Wave Jerks in Progressive Supranuclear Palsy

A Cortical Substrate for Square-Wave Jerks in Progressive Supranuclear Palsy

The Nigral Coup in Parkinson’s Disease by α-Synuclein and Its Associated Rebels

Shared cerebral metabolic pathology in non-transgenic animal models of Alzheimer's and Parkinson's disease

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