Human-specific gene ARHGAP11B—potentially an additional tool in the treatment of neurodegenerative diseases? DOI Creative Commons
Wieland Β. Huttner

Frontiers in Molecular Medicine, Journal Year: 2024, Volume and Issue: 4

Published: Nov. 27, 2024

One strategy in the treatment of neurodegenera=ve diseases has been towards replenishing lost cells, notably neurons. Approaches taken to this end have included following. First, either ac=vate neural stem cells that endogenously exist certain neurogenic niches adult human brain, such new neurons are being generated where needed (for recent reviews, see (Temple, 2023, Vassal et al., 2024, Velikic 2024)). Second, graS exogenous and/or exogenously into affected brain region, oSen by making use pa=ent-derived induced pluripotent (iPSCs) obtain former (Lee Temple, Vadodaria 2020)).In brief Opinion Ar=cle, I would like draw aXen=on human-specific gene ARHGAP11B, which exhibits proper=es could poten=ally be beneficial diseases.ARHGAP11B is typically referred as a gene. This statement correct with regard extant species, ARHGAP11B does not occur any other primate nor mammal. However, from an evolu=onary point view, actually homininspecific gene, it shown occurred Neandertals and Denisovans, light its origin ≈5 mya likely members Homo lineage review, (HuXner 2024)).A key feature addi=onal tool pertains cell types expressed. Thus, fetal neocortex, exhibi=ng highest level expression progenitor cells. Specifically, expressed both apical progenitors residing ventricular zone basal subventricular zone, radial glia (or outer) glia, respec=vely (Florio 2015). Such can seen strategic advantage if one intends cor=cal for therapeu=c approaches aim achieve replacement. Indeed, poten=al clinical relevance, various animal model systems vivo amplify progenitors, generate 2015, Kalebic 2018, Heide 2020, Xing 2021). Moreover, ARHGAP11B's effects on result increase neuron produc=on Of note, increases so-called upper-layer neurons, class implicated higher cogni=ve abili=es (Kalebic The amplifica=on based ability induce self-renewal 2020). Hence, fulfills criterion applica=on replenishment strategies -the induce, vivo, those neurons.To explore diseases, considered include following two. at targe=ng endogenous appropriate vector. Neural neurogenesis so far detected hippocampus (KempermannSong Gage, 2015)), amygdala (Roeder 2022), lateral ventricles summary, (Baig 2024). An vector should inducible on-off system first respec=ve switching thereaSer, upon off expression, allow them neurons.A second line approach make iPSCs converted then introduced. capacity administered region interest, followed local above.Should transient (i.e., inducible) indeed lead and, consequently, replenishment, future task will determine whether newly able func=onally compensate If so, forward-looking consider mechanism underlying protein imported matrix mitochondria expressing s=mulates metabolic pathway called glutaminolysis (Namba In emerging concept changes metabolism exert crucial impact behaviour 2021), specific pathways may aid endeavours diseases.

Language: Английский

Cancer neuroscience and glioma: clinical implications DOI Creative Commons
Manfred Westphal, Richard Drexler, Cécile L. Maire

et al.

Acta Neurochirurgica, Journal Year: 2025, Volume and Issue: 167(1)

Published: Jan. 3, 2025

Abstract In recent years, it has been increasingly recognized that tumor growth relies not only on support from the surrounding microenvironment but also tumors capacity to adapt – and actively manipulate its niche. While targeting angiogenesis modulating local immune environment have explored as therapeutic approaches, these strategies yet yield effective treatments for brain remain under refinement. More recently, nervous system itself a critical environmental cancer, with extensive neuro-tumoral interactions observed both intracranially in extracranial sites containing neural components. brain, between glioma cells well metastatic lesions components clinical implications diagnostics, risk assessments, neurological sequelae, development of innovative therapeutics. Here, we review dynamics, emphasizing aspects relevant neurosurgical practice.

Language: Английский

Citations

0
Brain aging and rejuvenation at single-cell resolution DOI Creative Commons
Eric Sun, Rahul Nagvekar, Angela N. Pogson

et al.

Neuron, Journal Year: 2025, Volume and Issue: 113(1), P. 82 - 108

Published: Jan. 1, 2025

SummaryBrain aging leads to a decline in cognitive function and concomitant increase the susceptibility neurodegenerative diseases such as Alzheimer's Parkinson's diseases. A key question is how changes within individual cells of brain give rise age-related dysfunction. Developments single-cell "omics" technologies, transcriptomics, have facilitated high-dimensional profiling cells. These technologies led new comprehensive characterizations at resolution. Here, we review insights gleaned from omics studies aging, starting with cell-type-centric overview age-associated followed by discussion cell-cell interactions during aging. We highlight provide an unbiased view different rejuvenation interventions comment on promise combinatorial approaches for brain. Finally, propose directions, including models neural stem focal point rejuvenation.

Language: Английский

Citations

0
Senescence Accelerated Mouse-Prone 8: a Model of Neuroinflammation and Aging with Features of Sporadic Alzheimer’s disease DOI Creative Commons
Jun Yi Ong, Kazunori Sasaki, Farhana Ferdousi

et al.

Stem Cells, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

Abstract The large majority of Alzheimer’s disease (AD) cases are sporadic with unknown genetic causes. In contrast, only a small percentage AD familial, known Paradoxically, there few validated mouse models but many familial AD. Senescence Accelerated Mouse-Prone 8 (SAMP8) mice model accelerated aging features They exhibit more complete suite human AD-relevant pathologies than most models. SAMP8 brains characterized by inflammation, glial activation, β-amyloid deposits, and hyperphosphorylated Tau. excess amyloid deposits congregate around blood vessels leading to vascular impairment leaky BBBs in these mice. also neuronal cell death, feature not typically seen Additionally, adult hippocampal neurogenesis is decreased correspondingly, they have reduced cognitive ability. line this, LTP significantly compromised No perfect limited the lack clarity about their genomic differences from control SAMR1 (Senescence Mouse-Resistant 1) although transcriptomics changes being revealed. To further complicate matters, multiple substrains emerged over years, sometimes making comparisons studies difficult. Despite challenges, we argue that can be useful for studying symptoms propose important experiments strengthen this already model.

Language: Английский

Citations

0
Structural pathways related to the subventricular zone are decreased in volume with altered microstructure in young adult males with autism spectrum disorder DOI
Keita Tsujimura, Alpen Ortuğ, José Luis Alatorre Warren

et al.

Cerebral Cortex, Journal Year: 2025, Volume and Issue: 35(3)

Published: March 1, 2025

Abstract Autism spectrum disorder is a neurodevelopmental condition characterized by reduced social communication and repetitive behaviors. Altered neurogenesis, including disturbed neuronal migration, has been implicated in autism disorder. Using diffusion MRI, we previously identified migration pathways the human fetal brain hypothesized that similar persist into adulthood, with differences volume microstructural characteristics between individuals controls. We analyzed MRI–based tractography of subventricular zone–related 15 young adult men 18 controls at Massachusetts General Hospital, validation through Imaging Data Exchange II dataset. Participants had zone pathway volumes fractional anisotropy compared to Furthermore, was positively correlated (r: 0.68; 95% CI: 0.25 0.88) symptom severity, suggesting more severe symptoms tended have larger volumes, normalized size. Analysis cohort confirmed these findings While some may potentially include inaccurately disconnected go zone, our results suggest MRI-based anatomically linked periventricular region are associated certain types males

Language: Английский

Citations

0
Lateral Ventricular Neural Stem Cells Provide Negative Feedback to Circuit Activation Through GABAergic Signaling DOI Creative Commons
Moawiah M. Naffaa, Henry H. Yin

Cells, Journal Year: 2025, Volume and Issue: 14(6), P. 426 - 426

Published: March 13, 2025

Recent studies have demonstrated that circuit activation in vivo can regulate proliferation of lateral ventricular neural stem cells (LV NSCs), although the underlying molecular and cellular mechanisms are not yet fully understood. Here, we investigated role GABAergic signaling interaction between LV NSCs anterior cingulate cortex-subependymal-choline acetyltransferase+ (ChAT+) neuron (ACC-subep-ChAT+) circuit. We found monoamine oxidase B (MAOB), a key enzyme involved gamma-aminobutyric acid (GABA) synthesis, is expressed NSCs, ACC-subep-ChAT+ modulate MAOB activity. Additionally, express LRRC8D, core component volume-regulated anion channels, GABA transporter-1 (GAT-1, SLC6A1). show evidence that, through signaling, LRRC8D GAT-1 provide negative feedback signal to ChAT+ neurons, NSCs. These findings suggest MAOB-driven LRRC8D-regulated chloride transport, GAT-1-facilitated reuptake influence NSC dynamics LV.

Language: Английский

Citations

0
Tools to study neural and glioma stem cell quiescence DOI
Dana Friess, Stephanie Brauer, Anni Pöysti

et al.

Trends in Neurosciences, Journal Year: 2024, Volume and Issue: 47(9), P. 736 - 748

Published: Aug. 26, 2024

Language: Английский

Citations

1
Spatiotemporal dynamics of the developing zebrafish enteric nervous system at the whole-organ level DOI
Can Li, Jase Gehring, Marianne Bronner‐Fraser

et al.

Developmental Cell, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 1, 2024

Language: Английский

Citations

1
APOE4 impacts cortical neurodevelopment and alters network formation in human brain organoids DOI Open Access

Karina K. Meyer-Acosta,

Eva Díaz‐Guerra, Parul Varma

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 7, 2024

Summary Apolipoprotein E4 ( APOE4 ) is the leading genetic risk factor for Alzheimer’s disease. While most studies examine role of in aging, imaging, and cognitive assessments reveal that influences brain structure function as early infancy. Here, we examined human-relevant cellular phenotypes across neurodevelopment using induced pluripotent stem cell (iPSC) derived cortical ganglionic eminence organoids (COs GEOs). In COs, showed decreased BRN2+ SATB2+ neurons, increased astrocytes outer radial glia, was associated with death dysregulated GABA-related gene expression. GEOs, accelerated maturation neural progenitors neurons. Multi-electrode array recordings assembloids revealed disrupted network formation altered response to GABA, resulting heightened excitability synchronicity. Together, our data provides new insights into how may influence neurodevelopmental processes human brain.

Language: Английский

Citations

0
Human-specific gene ARHGAP11B—potentially an additional tool in the treatment of neurodegenerative diseases? DOI Creative Commons
Wieland Β. Huttner

Frontiers in Molecular Medicine, Journal Year: 2024, Volume and Issue: 4

Published: Nov. 27, 2024

One strategy in the treatment of neurodegenera=ve diseases has been towards replenishing lost cells, notably neurons. Approaches taken to this end have included following. First, either ac=vate neural stem cells that endogenously exist certain neurogenic niches adult human brain, such new neurons are being generated where needed (for recent reviews, see (Temple, 2023, Vassal et al., 2024, Velikic 2024)). Second, graS exogenous and/or exogenously into affected brain region, oSen by making use pa=ent-derived induced pluripotent (iPSCs) obtain former (Lee Temple, Vadodaria 2020)).In brief Opinion Ar=cle, I would like draw aXen=on human-specific gene ARHGAP11B, which exhibits proper=es could poten=ally be beneficial diseases.ARHGAP11B is typically referred as a gene. This statement correct with regard extant species, ARHGAP11B does not occur any other primate nor mammal. However, from an evolu=onary point view, actually homininspecific gene, it shown occurred Neandertals and Denisovans, light its origin ≈5 mya likely members Homo lineage review, (HuXner 2024)).A key feature addi=onal tool pertains cell types expressed. Thus, fetal neocortex, exhibi=ng highest level expression progenitor cells. Specifically, expressed both apical progenitors residing ventricular zone basal subventricular zone, radial glia (or outer) glia, respec=vely (Florio 2015). Such can seen strategic advantage if one intends cor=cal for therapeu=c approaches aim achieve replacement. Indeed, poten=al clinical relevance, various animal model systems vivo amplify progenitors, generate 2015, Kalebic 2018, Heide 2020, Xing 2021). Moreover, ARHGAP11B's effects on result increase neuron produc=on Of note, increases so-called upper-layer neurons, class implicated higher cogni=ve abili=es (Kalebic The amplifica=on based ability induce self-renewal 2020). Hence, fulfills criterion applica=on replenishment strategies -the induce, vivo, those neurons.To explore diseases, considered include following two. at targe=ng endogenous appropriate vector. Neural neurogenesis so far detected hippocampus (KempermannSong Gage, 2015)), amygdala (Roeder 2022), lateral ventricles summary, (Baig 2024). An vector should inducible on-off system first respec=ve switching thereaSer, upon off expression, allow them neurons.A second line approach make iPSCs converted then introduced. capacity administered region interest, followed local above.Should transient (i.e., inducible) indeed lead and, consequently, replenishment, future task will determine whether newly able func=onally compensate If so, forward-looking consider mechanism underlying protein imported matrix mitochondria expressing s=mulates metabolic pathway called glutaminolysis (Namba In emerging concept changes metabolism exert crucial impact behaviour 2021), specific pathways may aid endeavours diseases.

Language: Английский

Citations

0