Shared and unique consequences of Joubert Syndrome gene dysfunction on the zebrafish central nervous system DOI Creative Commons
A. Noble, Markus Masek,

C. Hofmann

и другие.

Biology Open, Год журнала: 2024, Номер 13(11)

Опубликована: Окт. 14, 2024

ABSTRACT Joubert Syndrome (JBTS) is a neurodevelopmental ciliopathy defined by highly specific midbrain–hindbrain malformation, variably associated with additional neurological features. JBTS displays prominent genetic heterogeneity >40 causative genes that encode proteins localising to the primary cilium, sensory organelle essential for transduction of signalling pathways during neurodevelopment, among other vital functions. localise distinct ciliary subcompartments, suggesting diverse functions in cilium biology. Currently, there no unifying pathomechanism explain how dysfunction such cilia-related results brain abnormality. To identify shared consequence gene dysfunction, we carried out transcriptomic analysis using zebrafish mutants JBTS-causative cc2d2aw38, cep290fh297, inpp5ezh506, talpid3i264 and togaram1zh510 Bardet-Biedl syndrome-causative bbs1k742. We identified commonly dysregulated these yet all displayed an enrichment altered sets related central nervous system function. found have cilia throughout but do not display abnormal morphology. Nonetheless, behavioural analyses revealed reduced locomotion loss postural control which, together results, hint at underlying abnormalities neuronal activity and/or circuit These models therefore offer unique opportunity study role function beyond early patterning, proliferation differentiation.

Язык: Английский

Motile cilia modulate neuronal and astroglial activity in the zebrafish larval brain DOI Creative Commons
Percival P. D’Gama, Inyoung Jeong, Andreas Moe Nygård

и другие.

Cell Reports, Год журнала: 2025, Номер 44(1), С. 115195 - 115195

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

2
The Multifaceted Role of LRRK2 in Parkinson’s Disease DOI Creative Commons
Dong Hwan Ho,

Sun Jung Han,

Ilhong Son

и другие.

Brain Sciences, Год журнала: 2025, Номер 15(4), С. 407 - 407

Опубликована: Апрель 17, 2025

Leucine-rich repeat kinase 2 (LRRK2) is a multifunctional protein intricately involved in the pathogeneses of various neurodegenerative diseases, particularly Parkinson's disease (PD). LRRK2 plays pivotal role mitochondrial function and cellular senescence by regulating key processes such as autophagy, oxidative stress, aggregation. also associated with ciliogenesis neuronal development. In addition, has been implicated putative mediator neuroinflammation via promoting reactivation microglia influencing cytokine production, factor that may have therapeutic implications. Furthermore, mutations found to impact production neurotrophic factors astrocytes, star-shaped glial cells central nervous system, thereby affecting health contributing pathology diseases like PD. The multifaceted roles senescence, interaction LRS, neuroinflammation, maintenance mitochondria, astrocyte highlight its significance target for disorders.

Язык: Английский

Процитировано

0
Zebrafish in-vivo study reveals deleterious activity of human TBC1D24 genetic variants linked with autosomal dominant hearing loss DOI
Anna Sarosiak, Justyna Jędrychowska, Dominika Oziębło

и другие.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2024, Номер unknown, С. 167598 - 167598

Опубликована: Ноя. 1, 2024

Язык: Английский

Процитировано

0
Shared and unique consequences of Joubert Syndrome gene dysfunction on the zebrafish central nervous system DOI Creative Commons
A. Noble, Markus Masek,

C. Hofmann

и другие.

Biology Open, Год журнала: 2024, Номер 13(11)

Опубликована: Окт. 14, 2024

ABSTRACT Joubert Syndrome (JBTS) is a neurodevelopmental ciliopathy defined by highly specific midbrain–hindbrain malformation, variably associated with additional neurological features. JBTS displays prominent genetic heterogeneity >40 causative genes that encode proteins localising to the primary cilium, sensory organelle essential for transduction of signalling pathways during neurodevelopment, among other vital functions. localise distinct ciliary subcompartments, suggesting diverse functions in cilium biology. Currently, there no unifying pathomechanism explain how dysfunction such cilia-related results brain abnormality. To identify shared consequence gene dysfunction, we carried out transcriptomic analysis using zebrafish mutants JBTS-causative cc2d2aw38, cep290fh297, inpp5ezh506, talpid3i264 and togaram1zh510 Bardet-Biedl syndrome-causative bbs1k742. We identified commonly dysregulated these yet all displayed an enrichment altered sets related central nervous system function. found have cilia throughout but do not display abnormal morphology. Nonetheless, behavioural analyses revealed reduced locomotion loss postural control which, together results, hint at underlying abnormalities neuronal activity and/or circuit These models therefore offer unique opportunity study role function beyond early patterning, proliferation differentiation.

Язык: Английский

Процитировано

0