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  1. Book: Non-dopamine lesions in Parkinson's disease

    Halliday, Glenda M. / Barker, Roger A. / Rowe, Dominic B.

    2011  

    Author's details ed. by Glenda M. Halliday ; Roger A. Barker ; Dominic B. Rowe
    Keywords Parkinson Disease / physiopathology ; Parkinson Disease / complications ; Brain / pathology ; Dopamine
    Language English
    Size XXI, 314 S. : Ill., 24 cm
    Publisher Oxford Univ. Press
    Publishing place Oxford u.a.
    Publishing country Great Britain
    Document type Book
    Note Includes bibliographical references and index
    HBZ-ID HT016622251
    ISBN 978-0-19-537108-6 ; 0-19-537108-9
    Database Catalogue ZB MED Medicine, Health

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    In stock of ZB MED Cologne/Königswinter

    Shelf markLoan statusLocation
    2010 A 6317 order for loan Magazin

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  2. Article ; Online: The importance of patient-centred drug development for amyotrophic lateral sclerosis.

    Kiernan, Matthew C / Halliday, Glenda M / Rowe, Dominic B / Tan, Rachel H

    Neuropathology and applied neurobiology

    2023  Volume 49, Issue 6, Page(s) e12944

    MeSH term(s) Humans ; Amyotrophic Lateral Sclerosis/drug therapy ; Drug Development
    Language English
    Publishing date 2023-12-26
    Publishing country England
    Document type Letter
    ZDB-ID 80371-6
    ISSN 1365-2990 ; 0305-1846
    ISSN (online) 1365-2990
    ISSN 0305-1846
    DOI 10.1111/nan.12944
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  3. Article ; Online: Short tandem repeat expansions in

    Henden, Lyndal / Fearnley, Liam G / Southwood, Dean / Smith, Andrew / Rowe, Dominic B / Kiernan, Matthew C / Pamphlett, Roger / Bahlo, Melanie / Blair, Ian P / Williams, Kelly L

    Amyotrophic lateral sclerosis & frontotemporal degeneration

    2024  , Page(s) 1–4

    Abstract: In patients of Asian ancestry, a heterozygous CGG repeat expansion of >100 units ... ...

    Abstract In patients of Asian ancestry, a heterozygous CGG repeat expansion of >100 units in
    Language English
    Publishing date 2024-05-10
    Publishing country England
    Document type Journal Article
    ZDB-ID 2705049-X
    ISSN 2167-9223 ; 2167-8421
    ISSN (online) 2167-9223
    ISSN 2167-8421
    DOI 10.1080/21678421.2024.2348636
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  4. Article ; Online: C9orf72-Associated Dipeptide Repeat Expansions Perturb ER-Golgi Vesicular Trafficking, Inducing Golgi Fragmentation and ER Stress, in ALS/FTD.

    Sultana, Jessica / Ragagnin, Audrey M G / Parakh, Sonam / Saravanabavan, Sayanthooran / Soo, Kai Ying / Vidal, Marta / Jagaraj, Cyril Jones / Ding, Kunjie / Wu, Sharlynn / Shadfar, Sina / Don, Emily K / Deva, Anand / Nicholson, Garth / Rowe, Dominic B / Blair, Ian / Yang, Shu / Atkin, Julie D

    Molecular neurobiology

    2024  

    Abstract: Hexanucleotide repeat expansions (HREs) in the chromosome 9 open reading frame 72 (C9orf72) gene are the most frequent genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Both are debilitating neurodegenerative ... ...

    Abstract Hexanucleotide repeat expansions (HREs) in the chromosome 9 open reading frame 72 (C9orf72) gene are the most frequent genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Both are debilitating neurodegenerative conditions affecting either motor neurons (ALS) in the brain and spinal cord or neurons in the frontal and/or temporal cortical lobes (FTD). HREs undergo repeat-associated non-ATG (RAN) translation on both sense and anti-sense strands, generating five distinct dipeptide repeat proteins (DPRs), poly-GA, -GR, -GP, -PA and -PR. Perturbed proteostasis is well-recognised in ALS pathogenesis, including processes affecting the endoplasmic reticulum (ER) and Golgi compartments. However, these mechanisms have not been well characterised for C9orf72-mediated ALS/FTD. In this study we demonstrate that C9orf72 DPRs polyGA, polyGR and polyGP (× 40 repeats) disrupt secretory protein transport from the ER to the Golgi apparatus in neuronal cells. Consistent with this finding, these DPRs also induce fragmentation of the Golgi apparatus, activate ER stress, and inhibit the formation of the omegasome, the precursor of the autophagosome that originates from ER membranes. We also demonstrate Golgi fragmentation in cells undergoing RAN translation that express polyGP. Furthermore, dysregulated ER-Golgi transport was confirmed in C9orf72 patient dermal fibroblasts. Evidence of aberrant ER-derived vesicles in spinal cord motor neurons from C9orf72 ALS patients compared to controls was also obtained. These data thus confirm that ER proteostasis and ER-Golgi transport is perturbed in C9orf72-ALS in the absence of protein over-expression. Hence this study identifies novel molecular mechanisms associated with the ER and Golgi compartments induced by the C9orf72 HRE.
    Language English
    Publishing date 2024-05-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 645020-9
    ISSN 1559-1182 ; 0893-7648
    ISSN (online) 1559-1182
    ISSN 0893-7648
    DOI 10.1007/s12035-024-04187-4
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  5. Article ; Online: Heterogeneity of cortical pTDP-43 inclusion morphologies in amyotrophic lateral sclerosis.

    Tan, Rachel H / McCann, Heather / Shepherd, Claire E / Pinkerton, Monica / Mazumder, Srestha / Devenney, Emma M / Adler, Gabrielle L / Rowe, Dominic B / Kril, Jillian / Halliday, Glenda M / Kiernan, Matthew C

    Acta neuropathologica communications

    2023  Volume 11, Issue 1, Page(s) 180

    Abstract: Background: Despite the presence of significant cortical pTDP-43 inclusions of heterogeneous morphologies in patients diagnosed with amyotrophic lateral sclerosis (ALS), pathological subclassification is routinely performed in the minority of patients ... ...

    Abstract Background: Despite the presence of significant cortical pTDP-43 inclusions of heterogeneous morphologies in patients diagnosed with amyotrophic lateral sclerosis (ALS), pathological subclassification is routinely performed in the minority of patients with concomitant frontotemporal dementia (FTD).
    Objective: In order to improve current understanding of the presence and relevance of pathological pTDP-43 subtypes in ALS, the present study examined the pattern of cortical pTDP-43 aggregates in 61 ALS cases without FTD.
    Results: Based on the presence, morphology and composition of pTDP-43 pathology, three distinct ALS-TDP subtypes were delineated: (1) A predominant pattern of pTDP-43 granulofilamentous neuronal inclusions (GFNIs) and grains that were immuno-negative for p62 was identified in 18% of cases designated ALS-TDP type E; (2) neuronal cytoplasmic inclusions (NCIs) that were immuno-positive for both pTDP-43 and p62 were observed in 67% of cases assigned ALS-TDP type B; and (3) scarce cortical pTDP-43 and p62 aggregates were identified in 15% of cases coined ALS-TDP type SC (scarce cortical). Quantitative analyses revealed a significantly greater burden of pTDP-43 GFNI and grains in ALS-TDP type E. Principal component analysis demonstrated significant relationships between GFNIs, grains and ALS-TDP subtypes to support the distinction of subtypes E and B. No significant difference in age at death or disease duration was found between ALS-TDP subgroups to suggest that these subtypes represent earlier or later stages of the same disease process. Instead, a significantly higher ALS-TDP stage, indicating greater topographical spread of pTDP-43, was identified in ALS-TDP type E. Alzheimer's disease neuropathological change (ABC score ≥ intermediate) and Lewy body disease (Braak stage ≥ IV) was more prevalent in the ALS-TDP type SC cohort, which also demonstrated a significantly lower overall cognitive score.
    Conclusion: In summary, the present study demonstrates that ALS-TDP does not represent a single homogenous neuropathology. We propose the subclassification of ALS-TDP into three distinct subtypes using standard immuno-stains for pTDP-43 and p62 in the motor cortex, which is routinely sampled and evaluated for diagnostic neuropathological characterisation of ALS. We propose that future studies specify both clinicopathological group and pTDP-43 subtype to advance current understanding of the pathogenesis of clinical phenotypes in pTDP-43 proteinopathies, which will have significant relevance to the development of targeted therapies for this heterogeneous disorder.
    MeSH term(s) Humans ; Amyotrophic Lateral Sclerosis/pathology ; Frontotemporal Dementia/pathology ; DNA-Binding Proteins/genetics ; Neurons/pathology ; Phenotype
    Chemical Substances DNA-Binding Proteins
    Language English
    Publishing date 2023-11-13
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2715589-4
    ISSN 2051-5960 ; 2051-5960
    ISSN (online) 2051-5960
    ISSN 2051-5960
    DOI 10.1186/s40478-023-01670-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: RNA sequencing of peripheral blood in amyotrophic lateral sclerosis reveals distinct molecular subtypes: Considerations for biomarker discovery.

    Grima, Natalie / Liu, Sidong / Southwood, Dean / Henden, Lyndal / Smith, Andrew / Lee, Albert / Rowe, Dominic B / D'Silva, Susan / Blair, Ian P / Williams, Kelly L

    Neuropathology and applied neurobiology

    2023  Volume 49, Issue 6, Page(s) e12943

    Abstract: Aim: Amyotrophic lateral sclerosis (ALS) is a heterogeneous neurodegenerative disease with limited therapeutic options. A key factor limiting the development of effective therapeutics is the lack of disease biomarkers. We sought to assess whether ... ...

    Abstract Aim: Amyotrophic lateral sclerosis (ALS) is a heterogeneous neurodegenerative disease with limited therapeutic options. A key factor limiting the development of effective therapeutics is the lack of disease biomarkers. We sought to assess whether biomarkers for diagnosis, prognosis or cohort stratification could be identified by RNA sequencing (RNA-seq) of ALS patient peripheral blood.
    Methods: Whole blood RNA-seq data were generated for 96 Australian sporadic ALS (sALS) cases and 48 healthy controls (NCBI GEO accession GSE234297). Differences in sALS-control gene expression, transcript usage and predicted leukocyte proportions were assessed, with pathway analysis used to predict the activity state of biological processes. Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning algorithms were applied to search for diagnostic and prognostic gene expression patterns. Unsupervised clustering analysis was employed to determine whether sALS patient subgroups could be detected.
    Results: Two hundred and forty-five differentially expressed genes were identified in sALS patients relative to controls, with enrichment of immune, metabolic and stress-related pathways. sALS patients also demonstrated switches in transcript usage across a small set of genes. We established a classification model that distinguished sALS patients from controls with an accuracy of 78% (sensitivity: 79%, specificity: 75%) using the expression of 20 genes. Clustering analysis identified four patient subgroups with gene expression signatures and immune cell proportions reflective of distinct peripheral effects.
    Conclusions: Our findings suggest that peripheral blood RNA-seq can identify diagnostic biomarkers and distinguish molecular subtypes of sALS patients however, its prognostic value requires further investigation.
    MeSH term(s) Humans ; Amyotrophic Lateral Sclerosis/diagnosis ; Amyotrophic Lateral Sclerosis/genetics ; Neurodegenerative Diseases ; Australia ; Biomarkers ; Sequence Analysis, RNA
    Chemical Substances Biomarkers
    Language English
    Publishing date 2023-10-11
    Publishing country England
    Document type Journal Article
    ZDB-ID 80371-6
    ISSN 1365-2990 ; 0305-1846
    ISSN (online) 1365-2990
    ISSN 0305-1846
    DOI 10.1111/nan.12943
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  7. Article ; Online: Increased peripheral inflammation in asymptomatic leucine-rich repeat kinase 2 mutation carriers.

    Dzamko, Nicolas / Rowe, Dominic B / Halliday, Glenda M

    Movement disorders : official journal of the Movement Disorder Society

    2016  Volume 31, Issue 6, Page(s) 889–897

    Abstract: Background: We aimed to determine if peripheral or central inflammatory cytokines are altered in healthy subjects carrying a leucine-rich repeat kinase 2 (LRRK2) G2019S mutation, and thus genetically at risk of Parkinson's disease (PD). We also aimed to ...

    Abstract Background: We aimed to determine if peripheral or central inflammatory cytokines are altered in healthy subjects carrying a leucine-rich repeat kinase 2 (LRRK2) G2019S mutation, and thus genetically at risk of Parkinson's disease (PD). We also aimed to identify differences in inflammatory cytokines between LRRK2 G2019S-associated and idiopathic PD once the disease manifests.
    Methods: Participants were genetically screened and phenotyped, and biological samples were collected and stored by the Michael J. Fox Foundation LRRK2 Cohort Consortium. Serum samples and matching clinical data were obtained from 71 asymptomatic LRRK2 G2019S mutation carriers (CSF n = 25), 75 neurologically normal controls (CSF n = 22), 75 idiopathic PD patients (CSF n = 29), and 76 PD patients with a LRRK2 G2019S mutation (CSF n = 20). Inflammatory cytokines were measured using multiplex enzyme-linked immunosorbent assays.
    Results: Serum levels of interleukin 1 beta could discriminate asymptomatic LRRK2 G2019S mutation carriers from controls, with a high inflammatory subgroup of carriers identified. This subgroup was significantly higher in a number of PD-implicated pro-inflammatory cytokines. Once PD had manifest, LRRK2 G2019S patients were discriminated from idiopathic PD by higher serum platelet-derived growth factor, and higher CSF vascular endothelial growth factor and interleukin 8.
    Conclusions: The results suggest that peripheral inflammation is higher in a percentage of subjects carrying the LRRK2 G2019S mutation. Replication and longitudinal follow-up is required to determine whether the increased peripheral cytokines can predict clinical PD. Importantly, these biological changes were observed prior to the clinical manifestations thought to herald PD. © 2016 International Parkinson and Movement Disorder Society.
    Language English
    Publishing date 2016-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 607633-6
    ISSN 1531-8257 ; 0885-3185
    ISSN (online) 1531-8257
    ISSN 0885-3185
    DOI 10.1002/mds.26529
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  8. Article ; Online: CMS-01 Genetic testing for familial amyotrophic lateral sclerosis (ALS): insights and challenges.

    Crook, Ashley / Hogden, Anne / Mumford, Virginia / Blair, Ian P / Williams, Kelly L / Rowe, Dominic B

    Amyotrophic lateral sclerosis & frontotemporal degeneration

    2019  Volume 20, Issue sup1, Page(s) 327–347

    Abstract: Background: ...

    Abstract Background:
    Language English
    Publishing date 2019-11-08
    Publishing country England
    Document type Journal Article
    ZDB-ID 2705049-X
    ISSN 2167-9223 ; 2167-8421
    ISSN (online) 2167-9223
    ISSN 2167-8421
    DOI 10.1080/21678421.2019.1647002
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  9. Article ; Online: Riluzole is associated with decreasing neuritic plaque severity in amyotrophic lateral sclerosis.

    Mazumder, Srestha / McCann, Heather / D'Silva, Susan / Furlong, Sarah / Shepherd, Claire E / Kril, Jillian J / Halliday, Glenda M / Rowe, Dominic B / Kiernan, Matthew C / Tan, Rachel H

    Brain : a journal of neurology

    2022  Volume 146, Issue 3, Page(s) e17–e19

    MeSH term(s) Humans ; Riluzole ; Amyotrophic Lateral Sclerosis ; Plaque, Amyloid ; Neuroprotective Agents ; Excitatory Amino Acid Antagonists
    Chemical Substances Riluzole (7LJ087RS6F) ; Neuroprotective Agents ; Excitatory Amino Acid Antagonists
    Language English
    Publishing date 2022-12-21
    Publishing country England
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 80072-7
    ISSN 1460-2156 ; 0006-8950
    ISSN (online) 1460-2156
    ISSN 0006-8950
    DOI 10.1093/brain/awac467
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  10. Article ; Online: NEK1 and STMN2 short tandem repeat lengths are not associated with Australian amyotrophic lateral sclerosis risk.

    Grima, Natalie / Henden, Lyndal / Fearnley, Liam G / Rowe, Dominic B / D'Silva, Susan / Pamphlett, Roger / Adams, Lorel / Kiernan, Matthew C / Mazumder, Srestha / Timmins, Hannah C / Zoing, Margaret / Bahlo, Melanie / Blair, Ian P / Williams, Kelly L

    Neurobiology of aging

    2022  Volume 116, Page(s) 92–95

    Abstract: Sporadic amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a complex genetic architecture. The lengths of two short tandem repeats (STRs), at the NEK1 and STMN2 loci, were recently associated with ALS risk in cohorts of ... ...

    Abstract Sporadic amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a complex genetic architecture. The lengths of two short tandem repeats (STRs), at the NEK1 and STMN2 loci, were recently associated with ALS risk in cohorts of European descent. The STMN2 STR was proposed to be predictive of clinical features including the age of onset and disease duration in bulbar onset cases. We sought to investigate NEK1 and STMN2 STR lengths in a cohort of Australian sporadic ALS cases (n = 608) and neurologically healthy controls (n = 4689) of European ancestry. ExpansionHunter was used to determine NEK1 and STMN2 STR length genotypes from whole-genome sequencing data followed by PCR validation of predicted lengths. No significant association was identified between sporadic ALS risk and the length of either STR. Further, neither NEK1 nor STMN2 STR lengths were indicative of the age of onset or disease duration. We report that the NEK1 and STMN2 STRs were not associated with ALS risk or clinical features in this Australian sporadic ALS cohort.
    MeSH term(s) Amyotrophic Lateral Sclerosis/genetics ; Amyotrophic Lateral Sclerosis/metabolism ; Australia ; Humans ; Microsatellite Repeats ; NIMA-Related Kinase 1/genetics ; NIMA-Related Kinase 1/metabolism ; Neurodegenerative Diseases/genetics ; Neurodegenerative Diseases/metabolism ; Stathmin/genetics ; Stathmin/metabolism
    Chemical Substances STMN2 protein, human ; Stathmin ; NEK1 protein, human (EC 2.7.11.1) ; NIMA-Related Kinase 1 (EC 2.7.11.1)
    Language English
    Publishing date 2022-05-22
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 604505-4
    ISSN 1558-1497 ; 0197-4580
    ISSN (online) 1558-1497
    ISSN 0197-4580
    DOI 10.1016/j.neurobiolaging.2022.04.012
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