No Evidence of Early Developmental Delay in Juvenile‐Onset Huntington's Disease Patients DOI Creative Commons

Laurel R. Olson,

Susan E. Dickens,

Jordan L. Schultz

et al.

Movement Disorders Clinical Practice, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 7, 2024

Abstract Background Previous studies suggest that early developmental delay is a common feature of Juvenile‐Onset Huntington's disease (JOHD), with highest incidence in those very high CAG repeats (> 80). However, all reports JOHD are exclusively based on retrospective review medical charts. Comprehensive assessment birth history metrics may provide better insight into the question life development JOHD. Objective To explore prevalence prematurity, complications, low weight and patients comparison to control participants. Methods Parents gene‐non‐expanded (GNE) participants from Kids‐HD (n = 104) Kids‐JOHD 34, 24% > 80) completed comprehensive questionnaire. Answers focused weight, along milestones, were compared between groups. Results There no statistically significant differences weights, or motor verbal milestones GNE controls (all P values 0.1). Furthermore, stratifying by expansion (low vs. high) also showed (GNE high). Conclusions These findings support notion does not manifest as before symptom onset highlight new framework understand course nature disease.

Language: Английский

Inflammation and Huntington’s disease- a neglected therapeutic target? DOI Creative Commons

Sophie E. Field,

Annabel J. Curle, Roger A. Barker

et al.

Expert Opinion on Investigational Drugs, Journal Year: 2024, Volume and Issue: 33(5), P. 451 - 467

Published: May 3, 2024

Huntington's Disease (HD) is a genetic neurodegenerative disease for which there currently no disease-modifying treatment. One of several underlying mechanisms proposed to be involved in HD pathogenesis inflammation; now accumulating evidence that the immune system may play an integral role pathology and progression. As such, modulation could potential therapeutic target HD.

Language: Английский

Citations

5
Exploring functional dysconnectivity in schizophrenia: alterations in eigenvector centrality mapping and insights into related genes from transcriptional profiles DOI Creative Commons
Yuan Ji,

Mengjing Cai,

Yujing Zhou

et al.

Schizophrenia, Journal Year: 2024, Volume and Issue: 10(1)

Published: March 15, 2024

Schizophrenia is a mental health disorder characterized by functional dysconnectivity. Eigenvector centrality mapping (ECM) has been employed to investigate alterations in connectivity schizophrenia, yet the results lack consistency, and genetic mechanisms underlying these changes remain unclear. In this study, whole-brain voxel-wise ECM analyses were conducted on resting-state magnetic resonance imaging data. A cohort of 91 patients with schizophrenia matched healthy controls included during discovery stage. Additionally, replication stage, 153 individuals 182 participated. Subsequently, comprehensive analysis was performed using an independent transcriptional database derived from six postmortem adult brains explore potential factors influencing observed dysconnectivity, roles identified genes neural processes pathways. The revealed significant reliable across multiple brain regions schizophrenia. Specifically, there decrease bilateral superior middle temporal gyrus, increase thalamus both stages. Furthermore, 420 whose expression patterns related ECM, enriched mainly biological associated synaptic signaling transmission. Together, study enhances our knowledge pathways involved shedding light that may be linked dysconnectivity disorder.

Language: Английский

Citations

4
Disruption of structural connectome hierarchy in age-related hearing loss DOI Creative Commons

Yi Zhen,

Hongwei Zheng, Yi Zheng

et al.

Frontiers in Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: March 17, 2025

Age-related hearing loss (ARHL) is a common sensory disability among older adults and considered risk factor for the development of dementia. Previous work has shown altered brain connectome topology in ARHL, including abnormal nodal strength clustering coefficient. However, whether ARHL affects hierarchical organization structural how these alterations relate to transcriptomic signatures remain unknown. Here, we apply gradient mapping framework derived from diffusion magnetic resonance imaging. We focus on first three gradients that reflect distinct connectome, assess ARHL-related changes. find that, compared controls, patients exhibit widespread disruptions organization, spanning primary areas (e.g., somatomotor network) high-order association default mode network). Subsequently, by employing subcortical-weighted weighting cortical subcortical-cortical connectivity, observe show significantly connectivity left caudate, nucleus accumbens, right hippocampus, amygdala. Finally, investigate relationship between gene expression gradients. are associated with weighted profiles, relevant genes preferentially enriched inorganic ion transmembrane transport terms related regulating biological processes. Taken together, findings highlight hierarchy reveal relevance abnormalities, contributing richer understanding neurobiological substrates ARHL.

Language: Английский

Citations

0
Brain overlapping system-level architecture influenced by external magnetic stimulation and internal gene expression in AD-spectrum patients DOI

Weina Yao,

Xinle Hou,

Wenao Zheng

et al.

Molecular Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: April 4, 2025

Language: Английский

Citations

0
Therapeutic targeting of RNA for neurological and neuromuscular disease DOI Open Access
Jodi L. Bubenik,

Marina M. Scotti,

Maurice S. Swanson

et al.

Genes & Development, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 14, 2024

Neurological and neuromuscular diseases resulting from familial, sporadic, or de novo mutations have devasting personal, societal impacts. As the initial product of DNA transcription, RNA transcripts their associated ribonucleoprotein complexes provide attractive targets for modulation by increasing wild-type blocking mutant allele expression, thus relieving downstream pathological consequences. Therefore, it is unsurprising that many existing under-development therapeutics focused on targeting disease-associated as a frontline drug strategy these genetic disorders. This review focuses current range modalities using examples both dominant recessive neurological diseases.

Language: Английский

Citations

3
Pathomechanisms of behavioral abnormalities in Huntington disease: an update DOI
K. A. Jellinger

Journal of Neural Transmission, Journal Year: 2024, Volume and Issue: 131(9), P. 999 - 1012

Published: June 14, 2024

Language: Английский

Citations

2
Mutant Huntingtin Drives Development of an Advantageous Brain Early in Life: Evidence in Support of Antagonistic Pleiotropy DOI Creative Commons
Mohit Neema, Jordan L. Schultz, Douglas R. Langbehn

et al.

Annals of Neurology, Journal Year: 2024, Volume and Issue: 96(5), P. 1006 - 1019

Published: Aug. 8, 2024

Objective Huntington's disease (HD) is a neurodegenerative caused by triplet repeat expansion within the gene huntingtin ( HTT ). Antagonistic pleiotropy theory of aging that posits some genes, facilitating individual fitness early in life through adaptive evolutionary changes, also augment detrimental aging‐related processes. may explain positive pressure toward functionally advantageous brain development vulnerable to rapid degeneration. The current study investigated antagonistic HD using years‐to‐onset paradigm unique sample children and young adults at risk for HD. Methods Cognitive, behavioral, motor, structural measures from premanifest gene‐expanded (n = 79) nonexpanded 112) participants (6–21 years) Kids‐HD were examined. All group modeled mixed‐effects regression approach assess years‐to‐onset‐based changes while controlling normal growth. Simultaneously, structure–function associations Results Decades motor onset, showed significantly better cognitive, scores versus controls, along with larger cerebral volumes cortical features. After this initial peak, prolonged deterioration was observed both functional measures. Far positively correlated measures, supporting view advantages mediated differences. Interpretation Mutant drive than subserves superior early‐life function. These findings support HD, where drives advantage followed accelerated ANN NEUROL 2024;96:1006–1019

Language: Английский

Citations

2
The role of neuron-like cell lines and primary neuron cell models in unraveling the complexity of neurodegenerative diseases: a comprehensive review DOI
Kianoush Ghiasvand, Mehdi Amirfazli,

Parvaneh Moghimi

et al.

Molecular Biology Reports, Journal Year: 2024, Volume and Issue: 51(1)

Published: Sept. 28, 2024

Language: Английский

Citations

2
Unravelling the role of huntingtin: from neurodevelopment to neurodegeneration DOI Open Access
Jordan L. Schultz,

Mohit Neema,

Peg Nopoulos

et al.

Brain, Journal Year: 2023, Volume and Issue: 146(11), P. 4408 - 4410

Published: Oct. 10, 2023

This scientific commentary refers to ‘Genetic topography and cortical cell loss in Huntington’s disease link development neurodegeneration’ by Estevez-Fraga et al. (https://doi.org/10.1093/brain/awad275).

Language: Английский

Citations

5
Transcriptional patterns of brain structural abnormalities in CSVD-related cognitive impairment DOI Creative Commons
Haixia Mao, Min Xu, Hui Wang

et al.

Frontiers in Aging Neuroscience, Journal Year: 2024, Volume and Issue: 16

Published: Nov. 29, 2024

Brain structural abnormalities have been associated with cognitive impairment in individuals small cerebral vascular disease (CSVD). However, the molecular and cellular factors making different brain regions more vulnerable to CSVD-related remain largely unknown.

Language: Английский

Citations

1