GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Association of Locus Coeruleus and Substantia Nigra Pathology With Cognitive and Motor Functions in Patients With Parkinson Disease
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Neurology Vol. 97, No. 10 ( 2021-09-7), p. e1007-e1016
    Details
    In: Neurology, Ovid Technologies (Wolters Kluwer Health), Vol. 97, No. 10 ( 2021-09-7), p. e1007-e1016
    Abstract: To investigate the contribution of substantia nigra (SN) and locus coeruleus (LC) pathology to clinical signs and symptoms in Parkinson disease (PD) by applying neuromelanin-weighted imaging. Methods Forty-seven patients with PD and 53 matched controls underwent motor assessment, a neuropsychological test battery, and neuromelanin-weighted MRI. Patients with PD were enrolled after fulfilling the criteria for clinically established PD as defined by the Movement Disorders Society Clinical Diagnostic Criteria. Two independent raters identified SN and LC and calculated the contrast-to-noise ratio (CNR). Results The intrarater reliability demonstrated good reliability between raters with an intraclass correlation coefficient of 0.88 ( p 〈 0.001) and an interrater reliability of 0.80 ( p 〈 0.001). Both SN and LC CNRs were lower in patients with PD ( p ≤ 0.001) compared to controls. The CNR of SN but not of LC was strongly correlated with disease duration ( p ≤ 0.001). Neuromelanin pathology of the pars compacta–containing dorsolateral SN correlated with Movement Disorders Society–sponsored version of the Unified Parkinson’s Disease Rating Scale I, II, and III but not cognitive function. In contrast, neuromelanin pathology of LC was associated with cognitive function in all tested domains but not with motor impairment or activities of daily living. No such associations were present in controls. Conclusions Neuromelanin imaging of the SN and LC is well-suited to map neurodegeneration in PD. Neuromelanin pathology of the SN correlates with motor dysfunction whereas LC pathology is related to cognitive impairment. Neuromelanin-weighted imaging of the LC could thus serve as an imaging marker of executive and other cognitive dysfunction in PD. Classification of Evidence This study provides Class I evidence that neuromelanin-weighted imaging was associated with the severity of various signs and symptoms in patients with PD.
    Type of Medium: Online Resource
    ISSN: 0028-3878 , 1526-632X
    URL: Article
    DOI: 10.1212/WNL.0000000000012444
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Bi‐Allelic COQ4 Variants Cause Adult‐Onset Ataxia‐Spasticity Spectrum Disease
    Wiley ; 2022
    In:  Movement Disorders Vol. 37, No. 10 ( 2022-10), p. 2147-2153
    Details
    In: Movement Disorders, Wiley, Vol. 37, No. 10 ( 2022-10), p. 2147-2153
    Abstract: COQ4 codes for a mitochondrial protein required for coenzyme Q 10 (CoQ 10 ) biosynthesis. Autosomal recessive COQ4 ‐associated CoQ 10 deficiency leads to an early‐onset mitochondrial multi‐organ disorder. Methods In‐house exome and genome datasets (n = 14,303) were screened for patients with bi‐allelic variants in COQ4. Work‐up included clinical characterization and functional studies in patient‐derived cell lines. Results Six different COQ4 variants, three of them novel, were identified in six adult patients from four different families. Three patients had a phenotype of hereditary spastic paraparesis, two sisters showed a predominant cerebellar ataxia, and one patient had mild signs of both. Studies in patient‐derived fibroblast lines revealed significantly reduced amounts of COQ4 protein, decreased CoQ 10 concentrations, and elevated levels of the metabolic intermediate 6‐demethoxyubiquinone. Conclusion We report bi‐allelic variants in COQ4 causing an adult‐onset ataxia‐spasticity spectrum phenotype and a disease course much milder than previously reported. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
    Type of Medium: Online Resource
    ISSN: 0885-3185 , 1531-8257
    URL: Issue
    URL: Article
    DOI: 10.1002/mds.v37.10
    DOI: 10.1002/mds.29167
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2041249-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Neuroimaging in Primary Coenzyme-Q10-Deficiency Disorders
    MDPI AG ; 2023
    In:  Antioxidants Vol. 12, No. 3 ( 2023-03-14), p. 718-
    Details
    In: Antioxidants, MDPI AG, Vol. 12, No. 3 ( 2023-03-14), p. 718-
    Abstract: Coenzyme Q10 (CoQ10) is an endogenously synthesized lipid molecule. It is best known for its role as a cofactor within the mitochondrial respiratory chain where it functions in electron transfer and ATP synthesis. However, there are many other cellular pathways that also depend on the CoQ10 supply (redox homeostasis, ferroptosis and sulfide oxidation). The CoQ10 biosynthesis pathway consists of several enzymes, which are encoded by the nuclear DNA. The majority of these enzymes are responsible for modifications of the CoQ-head group (benzoquinone ring). Only three enzymes (PDSS1, PDSS2 and COQ2) are required for assembly and attachment of the polyisoprenoid side chain. The head-modifying enzymes may assemble into resolvable domains, representing COQ complexes. During the last two decades, numerous inborn errors in CoQ10 biosynthesis enzymes have been identified. Thus far, 11 disease genes are known (PDSS1, PDSS2, COQ2, COQ4, COQ5, COQ6, COQ7, COQ8A, COQ8B, COQ9 and HPDL). Disease onset is highly variable and ranges from the neonatal period to late adulthood. CoQ10 deficiency exerts detrimental effects on the nervous system. Potential consequences are neuronal death, neuroinflammation and cerebral gliosis. Clinical features include encephalopathy, regression, movement disorders, epilepsy and intellectual disability. Brain magnetic resonance imaging (MRI) is the most important tool for diagnostic evaluation of neurological damage in individuals with CoQ10 deficiency. However, due to the rarity of the different gene defects, information on disease manifestations within the central nervous system is scarce. This review aims to provide an overview of brain MRI patterns observed in primary CoQ10 biosynthesis disorders and to highlight disease-specific findings.
    Type of Medium: Online Resource
    ISSN: 2076-3921
    URL: Article
    DOI: 10.3390/antiox12030718
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2704216-9
    SSG: 15,3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Neuroinflammation and Mitochondrial Dysfunction in Parkinson’s Disease: Connecting Neuroimaging with Pathophysiology
    MDPI AG ; 2023
    In:  Antioxidants Vol. 12, No. 7 ( 2023-07-12), p. 1411-
    Details
    In: Antioxidants, MDPI AG, Vol. 12, No. 7 ( 2023-07-12), p. 1411-
    Abstract: There is a pressing need for disease-modifying therapies in patients suffering from neurodegenerative diseases, including Parkinson’s disease (PD). However, these disorders face unique challenges in clinical trial designs to assess the neuroprotective properties of potential drug candidates. One of these challenges relates to the often unknown individual disease mechanisms that would, however, be relevant for targeted treatment strategies. Neuroinflammation and mitochondrial dysfunction are two proposed pathophysiological hallmarks and are considered to be highly interconnected in PD. Innovative neuroimaging methods can potentially help to gain deeper insights into one’s predominant disease mechanisms, can facilitate patient stratification in clinical trials, and could potentially map treatment responses. This review aims to highlight the role of neuroinflammation and mitochondrial dysfunction in patients with PD (PwPD). We will specifically introduce different neuroimaging modalities, their respective technical hurdles and challenges, and their implementation into clinical practice. We will gather preliminary evidence for their potential use in PD research and discuss opportunities for future clinical trials.
    Type of Medium: Online Resource
    ISSN: 2076-3921
    URL: Article
    DOI: 10.3390/antiox12071411
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2704216-9
    SSG: 15,3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Table_2.docx
    Frontiers Media SA ; 2021
    In:  Frontiers in Cell and Developmental Biology Vol. 8 ( 2021-1-5)
    Details
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 8 ( 2021-1-5)
    Abstract: The underlying pathophysiology of Parkinson's disease is complex, but mitochondrial dysfunction has an established and prominent role. This is supported by an already large and rapidly growing body of evidence showing that the role of mitochondrial (dys)function is central and multifaceted. However, there are clear gaps in knowledge, including the dilemma of explaining why inherited mitochondriopathies do not usually present with parkinsonian symptoms. Many aspects of mitochondrial function are potential therapeutic targets, including reactive oxygen species production, mitophagy, mitochondrial biogenesis, mitochondrial dynamics and trafficking, mitochondrial metal ion homeostasis, sirtuins, and endoplasmic reticulum links with mitochondria. Potential therapeutic strategies may also incorporate exercise, microRNAs, mitochondrial transplantation, stem cell therapies, and photobiomodulation. Despite multiple studies adopting numerous treatment strategies, clinical trials to date have generally failed to show benefit. To overcome this hurdle, more accurate biomarkers of mitochondrial dysfunction are required to detect subtle beneficial effects. Furthermore, selecting study participants early in the disease course, studying them for suitable durations, and stratifying them according to genetic and neuroimaging findings may increase the likelihood of successful clinical trials. Moreover, treatments involving combined approaches will likely better address the complexity of mitochondrial dysfunction in Parkinson's disease. Therefore, selecting the right patients, at the right time, and using targeted combination treatments, may offer the best chance for development of an effective novel therapy targeting mitochondrial dysfunction in Parkinson's disease.
    Type of Medium: Online Resource
    ISSN: 2296-634X
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fcell.2020.615461
    DOI: 10.3389/fcell.2020.615461.s001
    DOI: 10.3389/fcell.2020.615461.s002
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2737824-X
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Utility and implications of exome sequencing in early‐onset Parkinson's disease
    Wiley ; 2019
    In:  Movement Disorders Vol. 34, No. 1 ( 2019-01), p. 133-137
    Details
    In: Movement Disorders, Wiley, Vol. 34, No. 1 ( 2019-01), p. 133-137
    Abstract: Although the genetic load is high in early‐onset Parkinson's disease, thorough investigation of the genetic diagnostic yield has yet to be established. The objectives of this study were to assess variants in known genes for PD and other movement disorders and to find new candidates in 50 patients with early‐onset PD. Methods We searched for variants either within genes listed by the International Parkinson and Movement Disorder Society Task Force on Genetic Nomenclature or rare homozygous variants in novel candidate genes. Further, exome data from 1148 European PD patients (International Parkinson Disease Genomics Consortium) were used for association testing. Results Seven patients (14%) carried pathogenic or likely pathogenic variants in Parkin, PLA2G6 , or GBA . In addition, rare missense variants in DNAJC13 :p.R1830C and in PPM1K :p.Y352C were detected. SPG7 :p.A510V and PPM1K :p.Y352C revealed significant association with PD risk ( P   〈  0.05). Conclusions Although we identified pathogenic variants in 14% of our early‐onset PD patients, the majority remain unexplained, and novel candidates need to be validated independently to better further evaluate their role in PD. © 2018 International Parkinson and Movement Disorder Society
    Type of Medium: Online Resource
    ISSN: 0885-3185 , 1531-8257
    URL: Issue
    URL: Article
    DOI: 10.1002/mds.v34.1
    DOI: 10.1002/mds.27559
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2041249-6
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    Genotype-driven therapeutic developments in Parkinson’s disease
    Springer Science and Business Media LLC ; 2021
    In:  Molecular Medicine Vol. 27, No. 1 ( 2021-12)
    Details
    In: Molecular Medicine, Springer Science and Business Media LLC, Vol. 27, No. 1 ( 2021-12)
    Abstract: Remarkable advances have been reached in the understanding of the genetic basis of Parkinson’s disease (PD), with the identification of monogenic causes (mPD) and a plethora of gene loci leading to an increased risk for idiopathic PD. The expanding knowledge and subsequent identification of genetic contributions fosters the understanding of molecular mechanisms leading to disease development and progression. Distinct pathways involved in mitochondrial dysfunction, oxidative stress, and lysosomal function have been identified and open a unique window of opportunity for individualized treatment approaches. These genetic findings have led to an imminent progress towards pathophysiology-targeted clinical trials and potentially disease-modifying treatments in the future. Main body of the manuscript In this review article we will summarize known genetic contributors to the pathophysiology of Parkinson’s disease, the molecular mechanisms leading to disease development, and discuss challenges and opportunities in clinical trial designs. Conclusions The future success of clinical trials in PD is mainly dependent on reliable biomarker development and extensive genetic testing to identify genetic cases. Whether genotype-dependent stratification of study participants will extend the potential application of new drugs will be one major challenge in conceptualizing clinical trials. However, the latest developments in genotype-driven treatments will pave the road to individualized pathophysiology-based therapies in the future.
    Type of Medium: Online Resource
    ISSN: 1076-1551 , 1528-3658
    URL: Article
    DOI: 10.1186/s10020-021-00281-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 1475577-4
    detail.hit.zdb_id: 1283676-X
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    Gene Therapeutic Approaches for the Treatment of Mitochondrial Dysfunction in Parkinson’s Disease
    MDPI AG ; 2021
    In:  Genes Vol. 12, No. 11 ( 2021-11-22), p. 1840-
    Details
    In: Genes, MDPI AG, Vol. 12, No. 11 ( 2021-11-22), p. 1840-
    Abstract: Background: Mitochondrial dysfunction has been identified as a pathophysiological hallmark of disease onset and progression in patients with Parkinsonian disorders. Besides the overall emergence of gene therapies in treating these patients, this highly relevant molecular concept has not yet been defined as a target for gene therapeutic approaches. Methods: This narrative review will discuss the experimental evidence suggesting mitochondrial dysfunction as a viable treatment target in patients with monogenic and idiopathic Parkinson’s disease. In addition, we will focus on general treatment strategies and crucial challenges which need to be overcome. Results: Our current understanding of mitochondrial biology in parkinsonian disorders opens up the avenue for viable treatment strategies in Parkinsonian disorders. Insights can be obtained from primary mitochondrial diseases. However, substantial knowledge gaps and unique challenges of mitochondria-targeted gene therapies need to be addressed to provide innovative treatments in the future. Conclusions: Mitochondria-targeted gene therapies are a potential strategy to improve an important primary disease mechanism in Parkinsonian disorders. However, further studies are needed to address the unique design challenges for mitochondria-targeted gene therapies.
    Type of Medium: Online Resource
    ISSN: 2073-4425
    URL: Article
    DOI: 10.3390/genes12111840
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527218-4
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    Applicability of optical coherence tomography angiography (OCTA) imaging in Parkinson’s disease
    Springer Science and Business Media LLC ; 2021
    In:  Scientific Reports Vol. 11, No. 1 ( 2021-03-09)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2021-03-09)
    Abstract: To evaluate the significance of motion artifacts in optical coherence tomography angiography (OCTA) images of patients with Parkinson’s disease (PD) and healthy controls. In this prospective, cross-sectional study subjects with medicated PD (ON) and healthy, age- and gender-matched volunteers were recruited. Participants underwent specific ophthalmological examinations, including OCTA. Angiograms of the superficial retinal capillary plexus were evaluated for the type and frequency of artifacts using a validated motion artifact score (MAS). A total of 30 PD patients (60 eyes), average disease duration of 9.61 ± 5.55 years, and 30 matched, healthy controls (60 eyes) were recruited. Twenty percent of all eyes had an eye disease, unknown to the participant, with a significant impact on OCTA results. After cleansing the dataset by excluding subjects with confounding ocular comorbidities 42 eyes of 28 PD patients and 53 eyes of 29 healthy controls were further evaluated. Overall MAS and all five subtypes of motion artifacts were comparable without significant differences between groups. OCTA can be used in treated PD patients (ON) without a significant increase in motion artifacts. Nevertheless, special attention should be paid to image quality during the acquisition of OCTA data, for which an experienced OCTA operator is useful.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-021-84862-x
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2615211-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 10
    Online Resource
    Online Resource
    Clinical MR imaging in Parkinson’s disease: How useful is the swallow tail sign?
    Wiley ; 2021
    In:  Brain and Behavior Vol. 11, No. 7 ( 2021-07)
    Details
    In: Brain and Behavior, Wiley, Vol. 11, No. 7 ( 2021-07)
    Abstract: With conventional MRI, no Parkinson's disease (PD)‐specific abnormalities can be detected. However, there is a critical need for accompanying neuroimaging markers to guide the diagnosis. With high‐resolution susceptibility‐weighted MRI (SWI) sequences, the imaging of nigrosome‐1 (N1) is possible. The so‐called swallow tail sign (STS) has been proposed as a suitable neuroimaging marker for the diagnosis of PD. Objectives To investigate whether the absence of the STS can be applied for distinguishing PD patients from healthy controls (HCs). Methods SWI images of 44 PD patients and 50 age‐ and gender‐matched HCs were investigated using a 3T MRI scanner. Two trained neuroradiologists blind‐rated the images and evaluated whether the STS was absent (1) on one side or (2) both sides of the participant's midbrain. Results Our results confirmed good interrater reliability comparable to previously published studies. However, we did not identify any group differences between PD patients and HCs. Measures of diagnostic values revealed overall poor diagnostic performance. Conclusions Even though previously stated, our study does not confirm the potential use of the STS as a supportive neuroimaging marker for PD in a clinical setting. In conclusion, there is a critical need for improvements in N1‐targeted MRI sequences and the development of advanced segmentation algorithms.
    Type of Medium: Online Resource
    ISSN: 2162-3279 , 2162-3279
    URL: Issue
    URL: Article
    DOI: 10.1002/brb3.v11.7
    DOI: 10.1002/brb3.2202
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2623587-0
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...