The role of neuroimaging in Parkinson’s disease

Bidesi, Natasha; Andersen, Ida Vang; Windhorst, Albert D.; Shalgunov, Vladimir; Herth, Matthias M.

doi:10.1111/jnc.15516

Cited by 76 publications

(33 citation statements)

References 326 publications

(368 reference statements)

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“…The present application describes a series of novel N-linked isoquinoline amides as LRRK2 inhibitors for the treatment of Parkinson’s disease. Further, the application discloses compounds, their preparation, use, pharmaceutical composition, and treatment. …”

Section: Discussionmentioning

confidence: 99%

Novel N-Linked Isoquinoline Amides as LRRK2 Inhibitors for Treating Parkinson’s Disease

Sabnis¹

2022

ACS Med. Chem. Lett.

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Section: Discussionmentioning

confidence: 99%

Novel N-Linked Isoquinoline Amides as LRRK2 Inhibitors for Treating Parkinson’s Disease

Sabnis¹

2022

ACS Med. Chem. Lett.

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“…In recent years, with the continuous progress in functional imaging technologies, an increasing number of studies have explored the mechanism of exercise for treating PD through neuroimaging technology ( Weingarten et al, 2015 ; Myers et al, 2018 ). Among them, functional MRI (fMRI) is widely used due to its advantages of being non-invasive, non-radioactive, and having a relatively high spatial resolution, which allows the study of PD to be extended to the level of brain function/neurotic material metabolism and to understand further the pathogenesis of PD motor and non-motor symptoms ( Bidesi et al, 2021 ; Mitchell et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Effects of Exercise on Parkinson’s Disease: A Meta-Analysis of Brain Imaging Studies

Guo

Sun

et al. 2022

Front. Hum. Neurosci.

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BackgroundExercise is increasingly recognized as a key component of Parkinson’s disease (PD) treatment strategies, but the underlying mechanism of how exercise affects PD is not yet fully understood.ObjectiveThe activation likelihood estimation (ALE) method is used to study the mechanism of exercise affecting PD, providing a theoretical basis for studying exercise and PD, and promoting the health of patients with PD.MethodsRelevant keywords were searched on the PubMed, Cochrane Library, and Web of Science databases. Seven articles were finally included according to the screening criteria, with a total sample size of 97 individuals. Using the GingerALE 3.0.2 software, an ALE meta-analysis was performed using seven studies that met the requirements, and the probability of the cross-experiment activation of each voxel was calculated.ResultsThe meta-analysis produced seven clusters, and major activations were found in the cerebellum, occipital lobe, parietal lobe, and frontal lobe brain regions.ConclusionExercise for PD mainly results in the enhanced activation of the cerebellum, occipital lobe, parietal lobe, and frontal lobe. Exercise for PD does not cause a change in the activation of a single brain area, and the observed improvement may result from coordinated changes in multiple brain areas.

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“…In addition, the eld is moving towards early eradication of α-synuclein aggregates as a promising therapeutic strategy in α-synucleinopathies, an approach that would require in vivo imaging for clinical application. As of today, no clinically validated PET radioligand exists for imaging α-synuclein [10,11].…”

Section: Introductionmentioning

confidence: 99%

“…11 C]MODAG-001 BP ND in different brain regions are shown in Figure 3A. BP ND in the 150 µg α-PFF regions was 0.78 ± 0.1 (mean±SD, n = 4) while in the 75 µg regions, BP ND α-PFF injected regions was 0.29 (n = 2), showing a dose-dependent effect of (d 3 )-[ 11 C]MODAG-001 binding to the α-PFF.…”

mentioning

confidence: 99%

Evaluation of the α-synuclein PET Radiotracer (d3)-[11C]MODAG-001 in Pigs

Raval

Madsen

Shalgunov

et al. 2022

Preprint

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Background:A positron emission tomography (PET) radiotracer to neuroimage α-synuclein aggregates would be a crucial addition for early diagnosis and treatment development in disorders such as Parkinson's disease, where elevated aggregate levels is a histopathological hallmark. The radiotracer (d3)-[11C]MODAG-001 has recently shown promise for visualization of α-synuclein pre-formed fibrils (α-PFF) in rodents. We here test the radiotracer in a pig model where proteins are intracerebrally injected immediately before scanning. Four pigs were injected in one hemisphere with 150 µg α-PFF, and in the other hemisphere, either 75 µg α-PFF or human brain homogenate from either dementia with Lewy bodies (DLB) or Alzheimer’s disease (AD) was injected. All pigs underwent one or two (d3)-[11C]MODAG-001 PET scans, quantified with the non-invasive Logan graphical analysis using the occipital cortex as a reference region.Results:The α-PFF and AD homogenate injected brain regions had high uptake of (d3)-[11C]MODAG-001 compared to the occipital cortex or cerebellum. BPND values in 150 µg α-PFF injected regions was 0.78, and in the AD homogenate injected regions was 0.73. By contrast, the DLB homogenate injected region did not differ in uptake and clearance compared to the reference regions. The time-activity curves and BPND values in the 150 µg and 75 µg injected region of α-PFFs show a dose-dependent effect, and the PET signal could be blocked by pretreatment with unlabeled MODAG-001. Conclusion:We find that both α-PFF and AD brain homogenates give rise to increased binding of (d3)-[11C]MODAG-001 when injected into the pig brain. Despite its limited specificity for cerebral α-synuclein pathology, (d3)-[11C]MODAG-001 shows promise as a lead tracer for future radiotracer development.

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The role of neuroimaging in Parkinson’s disease

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 76 publications

References 326 publications

Novel N-Linked Isoquinoline Amides as LRRK2 Inhibitors for Treating Parkinson’s Disease

Novel N-Linked Isoquinoline Amides as LRRK2 Inhibitors for Treating Parkinson’s Disease

Effects of Exercise on Parkinson’s Disease: A Meta-Analysis of Brain Imaging Studies

Evaluation of the α-synuclein PET Radiotracer (d3)-[11C]MODAG-001 in Pigs

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