Perinuclear compartment controls calcineurin/MEF2 signaling for axonal outgrowth of hippocampal neurons DOI Creative Commons
Joanna Mackiewicz, Malwina Lisek, Julia Tomczak

и другие.

Frontiers in Molecular Neuroscience, Год журнала: 2024, Номер 17

Опубликована: Ноя. 25, 2024

Central to the process of axon elongation is concept compartmentalized signaling, which involves A-kinase anchoring protein (AKAP)-dependent organization signaling pathways within distinct subcellular domains. This spatial also critical for translating electrical activity into biochemical events. Despite intensive research, detailed mechanisms by separation governs axonal outgrowth and pathfinding remain unresolved. In this study, we demonstrate that mAKAPα (AKAP6), located in perinuclear space primary hippocampal neurons, scaffolds calcineurin, NFAT, MEF2 transcription factors activity-dependent elongation. By employing disruptors, show mAKAPα/calcineurin/MEF2 pathway, but not drives outgrowth. Furthermore, mAKAPα-controlled linked changes expression genes involved Ca

Язык: Английский

Retinal ganglion cell repopulation for vision restoration in optic neuropathy: a roadmap from the RReSTORe Consortium DOI Creative Commons
Jonathan R. Soucy,

Erika A. Aguzzi,

Julie Cho

и другие.

Molecular Neurodegeneration, Год журнала: 2023, Номер 18(1)

Опубликована: Сен. 21, 2023

Retinal ganglion cell (RGC) death in glaucoma and other optic neuropathies results irreversible vision loss due to the mammalian central nervous system's limited regenerative capacity. RGC repopulation is a promising therapeutic approach reverse from if newly introduced neurons can reestablish functional retinal thalamic circuits. In theory, RGCs might be repopulated through transplantation of stem cell-derived or via induction endogenous transdifferentiation. The Repopulation, Stem Cell Transplantation, Optic Nerve Regeneration (RReSTORe) Consortium was established address challenges associated with repair visual pathway neuropathy. 2022, RReSTORe initiated ongoing international collaborative discussions advance field has identified five critical areas focus: (1) development differentiation, (2) Transplantation methods models, (3) survival, maturation, host interactions, (4) Inner wiring, (5) Eye-to-brain connectivity. Here, we discuss most pertinent questions that exist on path clinical translation suggest experimental directions propel this work going forward. Using these subtopic discussion groups (SDGs) as framework, multidisciplinary approaches restore diseased by leveraging groundbreaking insights developmental neuroscience, biology, molecular optical imaging, animal models neuropathy, immunology & immunotolerance, neuropathology neuroprotection, materials science biomedical engineering, neuroscience. While significant hurdles remain, Consortium's efforts provide comprehensive roadmap for advancing hold potential transformative progress restoring patients suffering neuropathies.

Язык: Английский

Процитировано

36

The neuroimmune interface in retinal regeneration DOI

Sucheta Bhattacharya,

Jugasmita Deka,

Thomas Avallone

и другие.

Progress in Retinal and Eye Research, Год журнала: 2025, Номер 106, С. 101361 - 101361

Опубликована: Апрель 24, 2025

Язык: Английский

Процитировано

0

Enhancing mitophagy by ligustilide through BNIP3-LC3 interaction attenuates oxidative stress-induced neuronal apoptosis in spinal cord injury DOI Creative Commons
Hui Yao, Chaoyang Cai, Weijun Huang

и другие.

International Journal of Biological Sciences, Год журнала: 2024, Номер 20(11), С. 4382 - 4406

Опубликована: Янв. 1, 2024

Mitophagy selectively eliminates damaged or dysfunctional mitochondria, playing a crucial role in maintaining mitochondrial quality control. However, it remains unclear whether mitophagy can be fully activated and how evolves after SCI. Our RNA-seq analysis of animal samples from sham 1, 3, 5, 7 days post-SCI indicated that was indeed inhibited during the acute subacute early stages.

Язык: Английский

Процитировано

3

Single-cell transcriptomics-enabled advances in experimental optic nerve axon regeneration research DOI
Ephraim F. Trakhtenberg

Elsevier eBooks, Год журнала: 2025, Номер unknown, С. 207 - 223

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0

Functional optic tract rewiring via subtype- and target-specific axonal regeneration and presynaptic activity enhancement DOI Creative Commons
Xin Zhang, Chao Yang, Chengle Zhang

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Март 4, 2025

Mechanisms underlying functional axonal rewiring after adult mammalian central nervous system (CNS) injuries remain unclear partially due to limited models. Here we develop a mouse intracranial pre-olivary pretectal nucleus (OPN) optic tract injury model and demonstrate that Pten/Socs3 knockout CNTF expression in retinal ganglion cells (RGCs) promotes regeneration OPN reinnervation. Revealed by transmission electron microscopy, trans-synaptic labeling, electrophysiology, synapses are formed mainly intrinsically photosensitive RGCs, thereby restoring the pupillary light reflex (PLR). Moreover, combining with Lipin1 knockdown accelerates recovery achieves reconnection chronic injury. PLR can be further boosted increasing RGC photosensitivity melanopsin overexpression, it also enhanced treatment of voltage-gated calcium channel modulator augment presynaptic release. These findings highlight importance neuronal types activity for CNS injuries.

Язык: Английский

Процитировано

0

See-through science: Danionella cerebrum as a model for neuroregeneration DOI

Mallika K Misyuk,

J Austin,

Noelle R Walechka

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Май 17, 2025

Rebuilding functional neuronal circuits after injury in the adult central nervous system (CNS) is unachievable for many vertebrates. In pro-regenerative models, it unclear how regeneration and re-wiring achieved CNS over long distances. The size opacity of vertebrate brain makes difficult to study axon topography dynamic cellular interactions during long-distance regeneration. Here, we harnessed properties small transparent Danionella cerebrum longitudinal vivo imaging retinal ganglion cell regeneration, correlating events with recovery. Our results suggest that some axons regenerate along tracts degenerating myelin debris. However, re-innervation different suggesting new are created restore vision. D. model provides a unique opportunity visualize experimentally manipulate spatial temporal intact

Язык: Английский

Процитировано

0

Axon guidance in central nervous system regeneration DOI
Brent Young, J. Goldberg

Developmental Cell, Год журнала: 2024, Номер 59(24), С. 3190 - 3192

Опубликована: Дек. 1, 2024

Язык: Английский

Процитировано

1

Emerging therapeutic strategies for optic nerve regeneration DOI Creative Commons
Qi Zhang, J. Tang, Liyan Liu

и другие.

Trends in Pharmacological Sciences, Год журнала: 2024, Номер 46(1), С. 45 - 61

Опубликована: Дек. 17, 2024

Язык: Английский

Процитировано

1

A p75 neurotrophin receptor‐sparing nerve growth factor protects retinal ganglion cells from neurodegeneration by targeting microglia DOI Creative Commons
Laura Latini, Daniel Souza Monteiro de Araújo, Rosario Amato

и другие.

British Journal of Pharmacology, Год журнала: 2024, Номер unknown

Опубликована: Сен. 9, 2024

Abstract Background and Purpose Retinal ganglion cells (RGCs) are the output stage of retinal information processing, via their axons forming optic nerve (ON). ON damage leads to axonal degeneration death RGCs, results in vision impairment. Nerve growth factor (NGF) signalling is crucial for RGC operations visual functions. Here, we investigate a new neuroprotective mechanism novel therapeutic candidate, p75‐less, TrkA‐biased NGF agonist (hNGFp) rat degeneration, comparison with wild type human (hNGFwt). Experimental Approach Both neonate adult rats, whether subjected or not lesion, were treated intravitreal injections eye drops containing either hNGFp hNGFwt. Different doses drugs administered at days 1, 4 7 after injury maximum 10 days, when immunofluorescence, electrophysiology, cellular morphology, cytokine array behaviour studies carried out. Pharmacokinetic evaluation was performed on rabbits ocular drops. Results exerted potent neuroprotection by acting microglia cells, outperformed hNGFwt rescuing reducing inflammatory molecules. Delayed use lesion resulted better outcomes compared treatment Moreover, hNGFp‐based less algogenic than measurements revealed that biologically relevant quantities found rabbit retina. Conclusions Implications Our data point as cell target through which NGF‐induced TrkA exerts RGC, emphasizing powerful tackle degeneration.

Язык: Английский

Процитировано

0

Chemogenetic neuronal silencing decouples c‐Jun activation from cell death in the temporal cortex DOI Open Access
Caleb A. Wood, Preethi Somasundaram, Jacob M. Dundee

и другие.

European Journal of Neuroscience, Год журнала: 2024, Номер unknown

Опубликована: Окт. 24, 2024

Abstract Initial symptoms of neurodegenerative diseases are often defined by the loss most vulnerable neural populations specific to each disorder. In early stages Alzheimer's disease, circuits in temporal lobe exhibit diminished activity prior overt degeneration. It remains unclear whether these functional changes contribute regional vulnerability or simply a consequence pathology. We previously found that entorhinal neurons cortex undergo cell death following transient suppression electrical activity, suggesting causal role for disruption neurodegeneration. Here we demonstrate arrest this circuit stimulates injury‐response transcription factor c‐Jun. Entorhinal silencing induces transcriptional consistent with c‐Jun activation share characteristics gene signatures other neuronal disease. Despite its established injury response, inhibiting failed ameliorate degeneration disruption. Finally, present preliminary evidence integrated stress response may serve as an alternative hypothesis what drives after silencing. Our data is activated but decoupled from subsequent

Язык: Английский

Процитировано

0