Synaptic vesicle endocytosis deficits underlie GBA-linked cognitive dysfunction in Parkinson′s disease and Dementia with Lewy bodies DOI Creative Commons
D. J. Vidyadhara, David Bäckström, Rajarshi Chakraborty

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 23, 2024

Abstract GBA is the major risk gene for Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB), two common α-synucleinopathies cognitive deficits. We investigated role of mutant in decline by utilizing Gba (L444P) mutant, SNCA transgenic (tg), Gba-SNCA double mice. Notably, mice showed early deficits but lacked PD-like motor or α-synuclein pathology. Conversely, tg displayed age-related deficits, without abnormalities. exhibited both exacerbated accompanied greater cortical phospho-α-synuclein pathology, especially layer 5 neurons. Single-nucleus RNA sequencing cortex uncovered synaptic vesicle (SV) endocytosis defects excitatory neurons mice, via robust downregulation genes regulating SV cycle synapse assembly. Immunohistochemistry electron microscopy validated these findings. Our results indicate that mutations, while exacerbating pre-existing aggregation contribute to through α-synuclein-independent mechanisms, involving dysfunction endocytosis.

Язык: Английский

Mechanisms of radiation‐induced tissue damage and response DOI Creative Commons

Zhou Lin,

Jiaojiao Zhu, Yuhao Liu

и другие.

MedComm, Год журнала: 2024, Номер 5(10)

Опубликована: Сен. 20, 2024

Radiation-induced tissue injury (RITI) is the most common complication in clinical tumor radiotherapy. Due to heterogeneity response of different tissues radiation (IR), radiotherapy will cause types and degrees RITI, which greatly limits application Efforts are continuously ongoing elucidate molecular mechanism RITI develop corresponding prevention treatment drugs for RITI. Single-cell sequencing (Sc-seq) has emerged as a powerful tool uncovering mechanisms identifying potential targets by enhancing our understanding complex intercellular relationships, facilitating identification novel cell phenotypes, allowing assessment spatiotemporal developmental trajectories. Based on comprehensive review we analyzed regulatory networks combination with Sc-seq summarized targeted intervention pathways therapeutic Deciphering diverse underlying can shed light its pathogenesis unveil new avenues potentially facilitate repair or regeneration currently irreversible Furthermore, discuss how personalized strategies based offer promise mitigating

Язык: Английский

Процитировано

5

New Multiomic Studies Shed Light on Cellular Diversity and Neuronal Susceptibility in Parkinson's Disease DOI Open Access
M H Liang, L. M. Chu, Zhenyu Yue

и другие.

Movement Disorders, Год журнала: 2025, Номер unknown

Опубликована: Янв. 15, 2025

Parkinson's disease is a complex neurodegenerative disorder characterized by degeneration of dopaminergic neurons, with patients manifesting varying motor and nonmotor symptoms. Previous studies using single-cell RNA sequencing in rodent models humans have identified distinct heterogeneity neurons glial cells differential vulnerability. Recent increasingly leveraged multiomics approaches, including spatial transcriptomics, epigenomics, proteomics, the study disease, providing new insights into pathogenic mechanisms. Continued advancements experimental technologies sophisticated computational tools will be essential uncovering network neuronal vulnerability prioritizing modifiers for novel therapeutics development. © 2025 International Parkinson Movement Disorder Society.

Язык: Английский

Процитировано

0

Sp3 ameliorated experimental autoimmune encephalomyelitis by triggering Socs3 in Th17 cells DOI Creative Commons
Yan Li, Mengyi Zhu, Penghui Yang

и другие.

Journal of Advanced Research, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0

Chromatin accessibility provides a window into the genetic etiology of human brain disease DOI
Jaroslav Bendl, John F. Fullard, Kiran Girdhar

и другие.

Trends in Genetics, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0

Genomic and Transcriptomic Approaches Advance the Diagnosis and Prognosis of Neurodegenerative Diseases DOI Open Access
Zheng Liu, Siyuan Song

Genes, Год журнала: 2025, Номер 16(2), С. 135 - 135

Опубликована: Янв. 24, 2025

Neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s (PD), Huntington’s (HD), and amyotrophic lateral sclerosis (ALS), represent a growing societal challenge due to their irreversible progression significant impact on patients, caregivers, healthcare systems. Despite advances in clinical imaging-based diagnostics, these diseases are often detected at advanced stages, limiting the effectiveness of therapeutic interventions. Recent breakthroughs genomic transcriptomic technologies, including whole-genome sequencing, single-cell RNA sequencing (scRNA-seq), CRISPR-based screens, have revolutionized field, offering new avenues for early diagnosis personalized prognosis. Genomic approaches elucidated disease-specific genetic risk factors molecular pathways, while studies identified stage-specific biomarkers that correlate with severity. Furthermore, genome-wide association (GWAS), polygenic scores (PRS), spatial transcriptomics enabling stratification patients based profiles prognostic trajectories. Advances functional genomics uncovered actionable targets, ATXN2 ALS TREM2 AD, paving way tailored strategies. achievements, challenges remain translating discoveries into practice heterogeneity complexity neurodegenerative pathophysiology. Future integration technologies holds promise transforming diagnostic paradigms, hope improved patient outcomes precision medicine approaches.

Язык: Английский

Процитировано

0

Mechanisms driving epigenetic and transcriptional responses of microglia in a neurodegenerative lysosomal storage disorder model DOI Open Access
Christopher Balak, Johannes C. M. Schlachetzki, Addison J. Lana

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 14, 2024

Lysosomal dysfunction is causally linked to neurodegeneration in many lysosomal storage disorders (LSDs) and associated with various age-related neurodegenerative diseases

Язык: Английский

Процитировано

1

Synaptic vesicle endocytosis deficits underlie GBA-linked cognitive dysfunction in Parkinson’s disease and Dementia with Lewy bodies DOI Creative Commons
Sreeganga S. Chandra, D. J. Vidyadhara, David Bäckström

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Дек. 27, 2024

GBA is the major risk gene for Parkinson's disease (PD) and Dementia with Lewy Bodies (DLB), two common α-synucleinopathies cognitive deficits. We investigated role of mutant in decline by utilizing Gba (L444P) mutant, SNCA transgenic (tg), Gba-SNCA double mice. Notably, mice showed early deficits but lacked PD-like motor or α-synuclein pathology. Conversely, tg displayed age-related deficits, without abnormalities. exhibited both exacerbated accompanied greater cortical phospho-α-synuclein pathology, especially layer 5 neurons. Single-nucleus RNA sequencing cortex uncovered synaptic vesicle (SV) endocytosis defects excitatory neurons mice, via robust downregulation genes regulating SV cycle synapse assembly. Immunohistochemistry electron microscopy validated these findings. Our results indicate that mutations, while exacerbating pre-existing aggregation contribute to through α-synuclein-independent mechanisms, involving dysfunction endocytosis.

Язык: Английский

Процитировано

1

Synaptic vesicle endocytosis deficits underlie GBA-linked cognitive dysfunction in Parkinson′s disease and Dementia with Lewy bodies DOI Creative Commons
D. J. Vidyadhara, David Bäckström, Rajarshi Chakraborty

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 23, 2024

Abstract GBA is the major risk gene for Parkinson’s disease (PD) and Dementia with Lewy Bodies (DLB), two common α-synucleinopathies cognitive deficits. We investigated role of mutant in decline by utilizing Gba (L444P) mutant, SNCA transgenic (tg), Gba-SNCA double mice. Notably, mice showed early deficits but lacked PD-like motor or α-synuclein pathology. Conversely, tg displayed age-related deficits, without abnormalities. exhibited both exacerbated accompanied greater cortical phospho-α-synuclein pathology, especially layer 5 neurons. Single-nucleus RNA sequencing cortex uncovered synaptic vesicle (SV) endocytosis defects excitatory neurons mice, via robust downregulation genes regulating SV cycle synapse assembly. Immunohistochemistry electron microscopy validated these findings. Our results indicate that mutations, while exacerbating pre-existing aggregation contribute to through α-synuclein-independent mechanisms, involving dysfunction endocytosis.

Язык: Английский

Процитировано

0