Cytotechnology, Год журнала: 2024, Номер 77(1)
Опубликована: Дек. 27, 2024
Язык: Английский
Translational Neurodegeneration, Год журнала: 2025, Номер 14(1)
Опубликована: Фев. 13, 2025
Язык: Английский
Процитировано
0
Trends in Molecular Medicine, Год журнала: 2025, Номер unknown
Опубликована: Фев. 1, 2025
Язык: Английский
Процитировано
0
npj Parkinson s Disease, Год журнала: 2025, Номер 11(1)
Опубликована: Март 17, 2025
Given the established association between numerous GBA1 variants and specific neurological diseases, we extended exploration by a phenome-wide study to assess impact of on wider spectrum health-related traits. We identified 41 phenotypes associated with variants, 39 which were unreported, including 21 non-neurological 20 phenotypes. Based variant-level tests, found beyond particularly decreased gray-white matter contrast measures across 13 distinct brain regions, non-coding variant rs9628662 was six traits such as hypermetropia. Another rs3115534 showed associations eight biomarkers multiple categories, an increased risk benign digestive neoplasms. Notably, compared protein-coding p.T408M, had opposing effects three hematological biomarkers. Additionally, gene-level analyses revealed significant diseases Parkinson's disease. The findings demonstrated that significantly various
Язык: Английский
Процитировано
0
Neurobiology of Disease, Год журнала: 2025, Номер unknown, С. 106899 - 106899
Опубликована: Апрель 1, 2025
Gaucher disease (GD), the most common lysosomal storage disorder, is an autosomal recessive inherited caused by mutations in GBA1. It can be categorized into neuronopathic and non-neuronopathic types. We previously constructed mouse models carrying Gba1 F213I point mutation tamoxifen-inducible systemic knockout mice, both of which developed rapidly had a short lifespan. This study combined these two to create Gba1flox/F213I; UBC-CreERT2 mice. These mice exhibited significantly extended lifespan, along with splenomegaly, infiltration Gaucher-like cells, reduced β-glucocerebrosidase (GCase) activity. Additionally, they displayed chronic neuroinflammation. In later stages, also typical pathological features Parkinson's (PD), including reduction dopaminergic neurons substantia nigra pars compacta (SNpc) increase expression levels α-synuclein (α-syn) protein. RNA sequencing (RNA-seq) from brain tissues revealed early, robust inflammatory response, particularly activation interferon pathway, downstream MHC I complex molecule genes, was confirmed through Western blot analysis. summary, we established neurogenic model that pronounced Parkinsonian-like phenotypes stages.
Язык: Английский
Процитировано
0
Genes, Год журнала: 2024, Номер 15(12), С. 1605 - 1605
Опубликована: Дек. 16, 2024
Parkinson’s disease (PD) is considered to be the second most prominent neurodegenerative and has a global prevalence. Glucocerebrosidase (GBA1) gene mutations represent significant hereditary risk factor for development of PD have profound impact on motor cognitive progression disease. The aim this review summarize literature data prevalence, type, peculiarities GBA1 in populations different ethnic backgrounds. We reviewed articles spanning 2000–2024 period. GBA1-related worldwide distribution. It long been recognized that pathogenic are particularly common certain populations, including patients Ashkenazi Jewish ancestry. Moreover, considerable number studies focused European ancestry from Europe North America revealed high proportion (up 15%) carriers among population. also appear play an important role patient groups with East Asian background, although frequency specific variants may differ as compared those Notably, assessment underrepresented other parts Asia (including India) Latin spotlight current research, while variant newly described mechanism reported Sub-Saharan Africans. Given importance genetics clinical phenotype, prevalence type distinct will possibly inform ongoing PD-related facilitate upcoming therapeutic trials.
Язык: Английский
Процитировано
2
Parkinsonism & Related Disorders, Год журнала: 2024, Номер 130, С. 107212 - 107212
Опубликована: Ноя. 19, 2024
Язык: Английский
Процитировано
1
medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Ноя. 22, 2024
Type 1 Tay-Sachs Disease (TSD) is a rare and severe neurodegenerative disorder caused by HEXA Loss of Function (LOF) gene mutations, leading to the accumulation lysosomal GM2 gangliosides progressive neurological decline, with high lethality before age 10. Current treatments are primarily palliative, focusing on symptom management. This study investigates therapeutic potential Miglustat Ambroxol, individually combined, in slowing neurodegeneration cognitive decline TSD, leveraging aiHumanoid virtual simulations. Miglustat, substrate reduction therapy, pharmacological chaperone, offer complementary mechanisms that may enhance function reduce ganglioside accumulation. In Phase 1b/2 trial, simulated cohorts children received these across four dose levels (10%, 20%, 33.3%, 50% maximum tolerated [MTD]), outcomes assessed at intervals from birth 10 years. Key metrics included motor function, quality life, enzyme activity. Results indicated combination therapy significantly reduced symptoms improved outcomes, particularly intermediate levels. Findings suggest Ambroxol provide beneficial intervention strategy, warranting further clinical evaluation. These results also important insights into optimization synergies, offering basis for real-world trials Disease. The use simulations demonstrates novel approach drug testing diseases, enabling detailed assessment efficacy safety profiles developmental stages. trial's findings based rather than traditional trials.
Язык: Английский
Процитировано
0
Genes, Год журнала: 2024, Номер 15(12), С. 1507 - 1507
Опубликована: Ноя. 25, 2024
As the global population ages, rising prevalence of neurodegenerative diseases, characterized by abnormal protein aggregates, presents significant challenges for early diagnosis and disease monitoring. Identifying accessible tissue biomarkers is crucial advancing our ability to detect track progression these diseases. Among most promising skin, which shares a common embryological origin with brain central nervous system (CNS). This biological connection positions skin as potential reflection CNS pathology. Over past decades, gene expression studies have demonstrated that key genes involved in diseases are also expressed tissues. Genes such
Язык: Английский
Процитировано
0
Cytotechnology, Год журнала: 2024, Номер 77(1)
Опубликована: Дек. 27, 2024
Язык: Английский
Процитировано
0